ALBERT

Beschreibung: Background: Statin-fibrate combination therapy has been used to treat patients with acute coronary syndrome (ACS) complicated by elevated triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C). The purpose of this study was to evaluate the influence of the combination therapy on lipids profile and apolipoprotein A5 (apoA5) level in patients with ACS. Methods: One hundred and four patients with ACS were recruited and randomly assigned into two groups: one was statin group (n = 52), given atorvastatin (20 mg QN) or other statins with equivalent dosages; the other was combination group (n = 52), given the same dose of statin plus bezafibrate (200 mg BID). Follow-up visits were scheduled at the end of 6 and 12 weeks post treatment. Serum apoA5 levels were determined using a commercial available ELISA kit. Results: (1) Compared with that of statin monotherapy, statin-bezafibrate combination treatment not only resulted in a significant reduction of TG, TC and LDL-C levels , (all p 〈 0.05), but also led to increases in HDL-C and apoA5 levels (p 〈 0.05).(2) The percentage changes of TC, TG, LDL-C and apoA5 levels in both groups were even bigger at 12 weeks after treatment than that at 6 weeks.(all p 〈 0.05). Similarly, the rates of achieving lipid-control target were higher in statin-bezafibrate combination treatment group than those in statin monotherapy group (all p 〈 0.05).(3) Spearman rank correlation analysis showed that the pre-treatment apoA5 level was positively correlated with TG (r = 0.359, p = 0.009). However, a negative correlation was observed between apoA5 and TG (r = -0.329, p = 0.017) after 12 weeks treatment. Conclusions: Statin and fibrate combination therapy is more effective than statin alone in achieving a comprehensive lipid control for ACS patients. Serum apoA5 elevation after statin and fibrate combination treatment could be due to the synergistic effect of both drugs on hypertriglyceridemia control.

Beschreibung: Background: Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. Methods: For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. Results: Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. Conclusions: In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.

Beschreibung: Background: The apolipoprotein M (APOM) T-778C gene polymorphism has been associated with serum lipid levels and the risk of coronary artery disease (CAD), but the results are inconclusive. The purpose of this meta-analysis was to detect the association between the APOM T-778C polymorphism and serum lipid levels and the risk of CAD in the Chinese population. Methods: Databases of MEDLINE, EMBASE, the Cochrane Library and CNKI were systematically searched. Data were extracted using standardized methods. The association was assessed by mean difference (MD) with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI. Results: Ten studies with 4,413 patients were included in this meta-analysis. Pooled effects indicated that CT+CC group had higher levels of total cholesterol (TC) (MD:-0.36, 95% CI: -0.53 -- -0.19, P 〈 0.0001) and low-density lipoprotein cholesterol (LDL-C) (MD: -0.08, 95% CI: -0.16 -- -0.01, P = 0.03) than TT group. There was no difference in the levels of triglyceride (MD: 0.06, 95% CI: -0.04 -- 0.15, P = 0.22) and high-density lipoprotein cholesterol (MD: 0.00, 95% CI: -0.03--0.03, P = 0.93) between TT and CT+CC groups. Pooled effects showed that CAD group had higher CT+CC genotype frequency than control group (OR: 1.97, 95% CI: 1.62--2.39, P 〈 0.00001; heterogeneity test x2 = 2.96, P = 0.71, I2 = 0%). Conclusions: The results of the current meta-analysis show that the CT+CC group has higher levels of TC and LDL-C than the TT group. Moreover, there is also a prominent association between APOM T-778C polymorphism and the risk of CAD in the Chinese population, the CT+CC genotype is associated with increased risk of CAD.

Beschreibung: Background: High consumption of fish carries a lower risk of cardiovascular disease as a consequence of dietary omega-3 long chain polyunsaturated fatty acid (n-3 PUFA; especially EPA and DHA) content. A controversy exists about the component/s responsible of these beneficial effects and, in consequence, which is the best proportion between both fatty acids. We sought to determine, in healthy Wistar rats, the proportions of EPA and DHA that would induce beneficial effects on biomarkers of oxidative stress, and cardiovascular disease risk. Methods: Female Wistar rats were fed for 13 weeks with 5 different dietary supplements of oils; 3 derived from fish (EPA/DHA ratios of 1:1, 2:1, 1:2) plus soybean and linseed as controls. The activities of major antioxidant enzymes (SOD, CAT, GPX, and GR) were determined in erythrocytes and liver, and the ORAC test was used to determine the antioxidant capacity in plasma. Also measured were: C reactive protein (CRP), endothelial dysfunction (sVCAM and sICAM), prothrombotic activity (PAI-1), lipid profile (triglycerides, cholesterol, HDLc, LDLc, Apo-A1, and Apo-B100), glycated haemoglobin and lipid peroxidation (LDL-ox and MDA values). Results: After three months of nutritional intervention, we observed statistically significant differences in the ApoB100/ApoA1 ratio, glycated haemoglobin, VCAM-1, SOD and GPx in erythrocytes, ORAC values and LDL-ox. Supplementation with fish oil derived omega-3 PUFA increased VCAM-1, LDL-ox and plasma antioxidant capacity (ORAC). Conversely, the ApoB100/ApoA1 ratio and percentage glycated haemoglobin decreased. Conclusions: Our results showed that a diet of a 1:1 ratio of EPA/DHA improved many of the oxidative stress parameters (SOD and GPx in erythrocytes), plasma antioxidant capacity (ORAC) and cardiovascular risk factors (glycated haemoglobin) relative to the other diets.

Beschreibung: Background: Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as gamma linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and alpha linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods: The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results: Supplementation with several EO/BO combinations increased circulating 20--22 carbon (20--22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by 〉50% and in stimulated neutrophils by 〉35%. Conclusions: This study shows that dietary supplementation with BO/EO alters 20--22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Beschreibung: Background: Atherosclerosis is a chronic progressive inflammatory disease of blood vessels particularly the arteries. The development of atherosclerotic plaques or atherogenesis is a complex process that is influenced by cardiovascular risk factors such as vascular inflammation and dyslipidemia. This study demonstrates the ability of tumor necrosis factor-alpha (TNF-alpha) and low density lipoproteins (LDL) to induce atherosclerotic plaque in human saphenous vein (HSV) organ culture. Methods: Normal HSV segments, from male patients who had coronary bypass graft, were cultured in DMEM containing 5% heat inactivated fetal bovine serum. TNF-alpha (5 ng/ml) was applied in combination with native LDL (nLDL) or oxidized LDL (oxLDL) at the dose of 50 mug/ml for 14 days. The phenotypic changes of the organ cultures characteristic of initial atherosclerotic plaques were evaluated. The effect of anti-atherogenic agent, 17-beta estradiol (E2), was also determined. Results: Histologic, histomorphometric, and immunohistochemical examinations revealed that HSV rings stimulated with TNF-alpha + nLDL or TNF-alpha + oxLDL can exhibit the essential morphological features of atherogenesis, including fibrous cap formation, cholesterol clefts, evident thickening of the intimal layer, increased proliferation of smooth muscle cells (SMC) and migration to the subendothelial layer, significant SMC foam cell formation, and increased expression of adhesion molecules in the vascular wall. Addition of E2 (50 nM) to the culture significantly modulated the critical changes. Consistently, mRNA profiling of the HSV model revealed that 50 of 84 genes of atherosclerosis were up-regulated. Conclusions: Phenotypic changes characteristic of the initial development of atherosclerotic plaques can be induced in HSV organ culture.

Beschreibung: Background: The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and / or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages. Methods: Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated. Results: In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats. Conclusions: Our data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats.

Beschreibung: Background: Although complex multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in hyperlipidemia which is a major risk factor for cardiovascular diseases. Therefore, here we investigated if a preparation developed for human use containing different vitamins, minerals and trace elements enriched with phytosterol (VMTP) affects the severity of experimental hyperlipidemia as well as myocardial ischemia/reperfusion injury. Methods: Male Wistar rats were fed a normal or cholesterol-enriched (2% cholesterol + 0.25% cholate) diet for 12 weeks to induce hyperlipidemia. From week 8, rats in both groups were fed with a VMTP preparation or placebo for 4 weeks. Serum triglyceride and cholesterol levels were measured at week 0, 8 and 12. At week 12, hearts were isolated, perfused according to Langendorff and subjected to a 30-min coronary occlusion followed by 120 min reperfusion to measure infarct size. Results: At week 8, cholesterol-fed rats showed significantly higher serum cholesterol level as compared to normal animals, however, serum triglyceride level did not change. VMTP treatment significantly decreased serum cholesterol level in the hyperlipidemic group by week 12 without affecting triglyceride levels. However, VMTP did not show beneficial effect on infarct size. The inflammatory marker hs-CRP and the antioxidant uric acid were also not significantly different. Conclusions: This is the first demonstration that treatment of hyperlipidemic subjects with a VMTP preparation reduces serum cholesterol, the major risk factor for cardiovascular disease; however, it does not provide cardioprotection.

Beschreibung: Background: C5L2, a G protein-coupled receptor (GPCR), has been demonstrated to be a ligand for acylation-stimulating protein (ASP). The aim of the present study is to evaluate the association of a novel variation (901A 〉 G) of C5L2 gene with coronary artery disease (CAD). Methods: We identified a novel single nucleotide polymorphism (SNP), (901G 〉 A), in exon 2 using a polymerase chain reaction direct-sequencing method. This nucleotide change causes the amino-acid order from Arginine to glutaminate at codon 300. We analyzed the relationship between this SNP and CAD in two independent case--control studies: one was in a Han population (492 CAD patients and 577 control subjects) and the other was in a Uygur population (319 CAD patients and 554 control subjects). Results: The frequency of AG genotype in CAD subjects was less than that in the control subjects not only in Han (1.8% vs 8.6%, P 〈 0.001, OR = 0.143, 95% CI: 0.068 ~ 0.302) but also in Uygur population (0.9% vs 5.2%, P = 0.001, OR = 0.246, 95% CI: 0.072 ~ 0.837). After adjustment for known CAD risk factors such as hypertension, diabetes, smoking, age and gender, the difference remained significant. Conclusion: The 901G 〉 A polymorphism of C5L2 may be a genetic maker of CAD in the Han and Uygur population in western China.

Beschreibung: Background: This study aimed to determine the relationship between dyslipidemia and dry eye disease (DED) in a Korean population. Methods: This population-based study enrolled 5,627 adults (aged 〉19 years) who were participating in the first year of the fifth annual Korea National Health and Nutrition Examination Survey from 2010 to 2011. Clinically diagnosed DED and its symptoms were surveyed, and biochemical blood analysis data were collected. Dyslipidemia was defined as any of the following: hypercholesterolemia (total cholesterol 〉 200 mg/dL), hypertriglyceridemia (triglyceride 〉 150 mg/dL), low levels of high-density lipoprotein ( 100 mg/dL). Results: After adjusting for demographics (age and body mass index), lifestyle (smoking, drinking, exercise, and residential district), and medical factors (diabetes, hypertension, previous ophthalmic surgery, menopause, and rheumatologic disease), elevated serum cholesterol level was found to be associated with increased likelihood of DED (odds ratio, 1.77; 95% confidence interval, 1.127--2.78) in women. Conclusions: DED in a Korean population was found to be associated with high serum cholesterol levelsThe results of this study highlight the significance of eye examinations and independent lipid profile monitoring in patients with dyslipidemia because of its possible correlation with DED progression.

Beschreibung: Background: Hyperlipidaemia is a major risk factor for coronary artery disease (CAD) and cholesteryl ester transfer protein (CETP) gene polymorphisms are known to be associated with lipid profiles. Methods: In this study, we investigated the association of two polymorphisms in the CETP, Taq1B (rs708272) and -629C 〉 A (rs1800775), with CAD and lipid levels HDL-C in 662 CAD + cases and 927 controls from the Singapore population comprising Chinese, Malays and Indians. Results: TaqB2 frequency was significantly lowest in the Malays (0.43) followed by Chinese (0.47) and highest in the Indians (0.56) in the controls. The B2 allele frequency was significantly lower in the Chinese CAD + cases compared to the controls (p = 0.002). The absence of the B2 allele was associated with CAD with an OR 2.0 (95% CI 1.2 to 3.4) after adjustment for the confounding effects of age, smoking, BMI, gender, hypertension, dyslipidemia and diabetes mellitus. The B2 allele was significantly associated with higher plasma HDL-C levels in the Chinese men after adjusting for confounders. Associations with plasma apoA1 levels were significant only in the Chinese men for Taq1B and -629C 〉 A. In addition, the Taq1B polymorphism was only associated with plasma Apo B and Lp(a) in the Malay men. Significant associations were only found in non-smoking subjects with BMI A polymorphisms seemed to be weak. Conclusion: The absence the Taq1B2 allele was associated with CAD in the Chinese population only and the minor allele of the Taq1B polymorphism of the CETP gene was significantly associated with higher plasma HDL-C levels in Chinese men.

Beschreibung: Background: Delayed wound healing is considered one of the most serious diabetes-associated complications. The presence of replicating organisms such as bacteria within a diabetic's wound is considered one of the most important factors that impair cutaneous wound healing and the potential cellular and/or molecular mechanisms that are involved in the healing process. Defensins, which are anti-microbial peptides, have potent bactericidal activity against a wide spectrum of the bacterial and fungal organisms that are commonly responsible for wound infections. We recently demonstrated that camel whey proteins (WPs) expedite the healing of diabetic wounds by enhancing the immune response of wounded tissue cells and by alleviating some of the diabetic complications. Methods: In the present study, we investigated the effects of WP supplementation on the mRNA and protein expression levels of beta-defensin-1 (BD-1), 2 and 3 and subsequently on the wound healing process in a streptozotocin (STZ)-induced diabetic mouse model. In this study, three groups of mice were used (10 mice per group): group 1, the non-diabetic mice (control); group 2, the diabetic mice; and group 3, the diabetic mice that received a daily supplement of undenatured WP (100 mg/kg of body weight) via oral gavage for 1 month. Results: Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound closure that was characterized by a reduction in hydroxyproline content (indicator of collagen deposition), a marked elevation in free radical levels and a prolonged elevation in the levels of inflammatory cytokines, including interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). Interestingly, compared with the diabetic mice that did not receive WP supplementation, the diabetic mice with WP had an accelerated closure and healing process of their wounds. The WP supplementation also decreased their levels of free radicals and restored their hydroxyproline content; proinflammatory cytokine levels; and expression of BD-1, 2 and 3 in the wounded tissue. Conclusion: WP supplementation may be beneficial for improving the healing and closure of diabetic wounds.

Beschreibung: Background: Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins. Methods: The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels 〉=80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment. Results: The percent change of LDL-C was -32% in the combination group and -14% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level

Beschreibung: ObjectiveTo investigate the influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet. Methods: Twenty-four male Wistar rats were randomly divided into 3 groups of 8: normal, model and intervention. The model group and intervention group were fed with high fat diet, while the normal group received basal feed. From day 1, the intervention group was randomly given interventions such as swimming exercise and dietary restriction. The interventions duration were 28 days. At the end of the experiment, the levels of rats' body weight and liver weight were detected, the serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and hepatic triglyceride content (TG) were detected by using biochemical assay, serum level of gastrin (GAS), motilin (MTL) were assayed by the enzyme linked immunosorbent assay (ELISA). Results: Compared with the level of body weight and liver weight in the normal rats, body weight and liver weight in the rat of the model group were significantly increase(P

Beschreibung: Background: Dried blood spots (DBS) from fingertip prick blood can enable high throughput fatty acid profiling but may be prone to lipid peroxidation during storage. The use of butylated hydroxytoluene (BHT) on chromatography paper can prevent polyunsaturated fatty acids (PUFA) loss but examinations on the length of storage time possible are not comprehensive.MethodIn the first study, venous whole blood was saturated on paper strips pre-soaked with 0, 2.5 or 5.0 mg/mL BHT and exposed to air for up to 28 days. In a second study, the effect of sealing DBS on 5.0 mg/mL BHT-soaked chromatography strips in capped test tubes or vacuum sealed polypropylene bags with and without nitrogen purging was examined over eight weeks. The fatty acid composition of the DBS were determined by gas chromatography and the effect of sample storage on omega-3 biomarkers were examined. Results: PUFA and omega-3 biomarkers in DBS stored without BHT were dramatically reduced by day 3. In general, BHT delayed decreases in eicosapentaenoic + docosahexaenoic acid from baseline (3.2 +/- 0.2 wt%) to 28 days (2.6 +/- 0.03 wt%) of storage. In the % n-3 highly unsaturated fatty acids (HUFA) in total HUFA biomarker, BHT was more effective at preventing changes, particularly with 5.0 mg/mL BHT where no differences were detected up to 28 days. Sealed storage with BHT tended to increase the stability of the PUFA in DBS and nitrogen purging did not appear to provide additional benefits. The % n-3 HUFA in total HUFA biomarker also appeared to be more stable in the sealed storage study. Conclusions: The storage of DBS in sealed containers with BHT may prevent PUFA degradation for up to 8 weeks. The % n-3 HUFA in total HUFA biomarker appears to provide a more consistent assessment of omega-3 status throughout storage as compared with other omega-3 blood biomarkers.

Beschreibung: Background: Mutation in SCARB1 gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans though the results have been inconsistent. We analysed the impact of SCARB1 single nucleotide polymorphism (SNP) rs5888 with plasma lipid profile and association with coronary artery disease (CAD) in a Lithuanian population characterized by high morbidity and mortality from CAD and high prevalence of hypercholesterolemia. Methods: The study included 1976 subjects from a random sample (reference group) and an myocardial infarction (MI) group of 463 patients. Genotyping of SCARB1 (rs5888) was carried out using the real-time polymerase chain reaction method.Results/principal findings: Analysis of rs5888 C/T gene polymorphism in the reference group revealed that male TT genotype carriers (25--74 years) had significantly higher total cholesterol and triglyceride concentrations (5.70 mmol/l vs. 5.49 mmol/l; p = 0.036, and 1.70 mmol/l vs. 1.40 mmol/l, p = 0.023, respectively) than CT carriers and the oldest males (65--74 years) TT carriers had significantly higher high density lipoprotein cholesterol concentrations in comparison to heterozygous (1.52 mmol/l vs. 1.36 mmol/l, p = 0.033). The youngest female (25--44 years) TT genotype carriers had significantly lower low density lipoprotein cholesterol concentrations in comparison to C homozygous (2.59 mmol/l vs. 2.92 mmol/l, p = 0.023). The frequency of the SCARB1 TT genotype in the oldest male MI group (65--74 years) was significantly lower than in the corresponding reference group subjects (9.4% vs. 22.3%, p = 0.006). SCARB1 TT genotype was associated with decreased odds of MI in males aged 65--75 years (OR = 0.24, 95% CI 0.10-0.56, p = 0.001).Conclusions/significance: SCARB1 polymorphism is associated with lipid metabolism and CAD in an age- and gender- dependent manner. Analysis of SCARB1 SNP rs5888 C/T genotypes revealed an atheroprotective phenotype of lipid profile in older men and in young women TT genotype carriers in the reference group. SCARB1 TT genotype was associated with decreased odds of MI in aged men.

Beschreibung: Background: HDL function rather than absolute level may be a more accurate indicator for risk of developing atherosclerosis. Dysfunctional HDL has increased redox activity and reduced antioxidant properties, but it is unknown whether abnormal HDL function is associated with progression of atherosclerosis in HIV-1-infected subjects.FindingsWe retrospectively measured serum HDL function in 91 subjects from a prospective 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1-uninfected (n=36) or HIV-1+ with (n=29) or without (n=26) protease inhibitor (PI)-based therapy for 〉= 2 years. HDL function was assessed using a biochemical assay that measures the oxidation of dihydrorhodamine 123 (DHR oxidation rate, DOR), in which higher DOR readout corresponds to dysfunctional HDL phenotype.There were no significant associations between DOR and HIV-1 infection. In univariate analysis of 55 HIV-1-infected subjects, greater waist circumference and lower serum HDL were significantly associated with higher baseline levels of DOR (p=0.01). These subjects had significant increases in levels of DOR over time (3 years) that were associated with white race (p=0.03), higher nadir CD4 count (p

Beschreibung: Background: Previous experimental investigations have suggested that guarana (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guarana on LDL and serum oxidation. Methods: The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guarana (GI) or never ingested guarana (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guarana in their diets. The LDL samples were exposed to 5 different guarana concentrations (0.05, 0.1, 0.5, 1, and 5 mug/mL). Results: GI subjects demonstrated lower LDL oxidation than did NG subjects (reduction of 27 %, p 〈 0.0014), independent of other variables. In the GI group the total polyphenols was positively associated with LDL levels. Also, guarana demonstrated a high antioxidant activity in vitro, mainly at concentrations of 1 and 5 mug/mL, demonstrated by suppression of CDs and TBARS productions, tryptophan destruction and high TRAP activity. Conclusions: Guarana, similar to other foods rich in caffeine and catechins such as green tea, has some effect on LDL oxidation that could partially explain the protective effects of this food in cardiometabolic diseases.

Beschreibung: This study was intended to explore the effect of extruded flaxseed meal supplemented diet on broiler growth performance, oxidative stability and organoleptic characteristics of broiler meat and meat products. 120 (day old) broiler chicks were randomly allotted to 12 experimental groups and fed on diets containing extruded flaxseed meal at 0, 5, 10 and 15%. The supplementation of extruded flaxseed in the diet decreases the body weight gain, feed intake and increased feed conversion ratio (FCR) values of broilers. The antioxidant enzymes were strongly influenced by different levels of extruded flaxseed supplementation among treatments. The TBARS assay revealed that maximum malondialdehyde were produced in T3 containing highest extruded flaxseed level (15%) and minimum malondialdehyde were produced in T0 treatment having no extruded flaxseed. The TBARS values ranged from 0.850-2.106 and 0.460-1.052 in leg and breast met respectively. The Free radical scavenging activity varied significantly and DPPH values of breast meat ranged from 20.70% to 39.09% and in leg meat 23.53% to 43.09 % respectively. The sensory acceptability of broiler meat nuggets was decreased with the increase in the level of flaxseeds due to the lipid peroxidation of polyunsaturated fatty acids (PUFA) which generated off flavors and bad odors. Feeding extruded flaxseed to chicken through feed strongly inflated the quality and functional properties, fatty acid contents and reduced the oxidative stability of broiler meat and meat products. The present study concludes that up to 10% of flaxseed meal may be used in broiler diet to enhance the omega 3 fatty acids content in the broiler meat.

Beschreibung: Background: Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. Methods: Sixteen male patients with T1DM (26 +/- 7 yrs) with glycated hemoglobin 〉7%, and 15 control subjects (28 +/- 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with 14C-cholesteryl ester and 3H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. Results: LDL-cholesterol (83 +/- 15 vs 100 +/- 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 +/- 0.022 vs 0.039overnight fast, blood samples were taken and +/- 0.022 h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. Conclusion: T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.

Beschreibung: Background: Postprandial lipemia (PL) in adults has been extensively studied, but little explored in youth. The aim of this study was to evaluate the influence of weight excess on postprandial lipemia in adolescents. Methods: Eighty-three adolescents were classified into Groups 1 (n= 49, overweight) and 2 (n=34, eutrophic). Total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol were measured before, 2 and 4 hours after a standardized 25 g lipid and 25 g of carbohydrate test meal; glycemia and insulin measured only at baseline. Anthropometric evaluation was performed. Results: Basal TG were higher in Group 1 (p= 0.022). The total increase ([increment]-TG), corresponding to the difference between the maximum and the basal TG level was similar in both groups (29.8 +/- 21.5 mg/dl vs. 28.2 +/- 24.5 mg/dl, p= 0.762). TC, HDL and LDL did not change significantly throughout the test. By analyzing all the adolescents together, the waist circumference was positively correlated with TG at fasting (r = 0.223; p= 0.044) and at 4 hours (r = 0.261; p= 0.019). Only overweight adolescents with hypertriglyceridemia, who also had higher HOMA-IR, presented significant elevation of TG levels 2 and 4 hours after the overload. Conclusion: The behavior of lipoproteins in the post-prandial state is similar in eutrophic and overweight adolescents. Thus, apparently the weight excess does not induce post prandial lipemic alterations.

Beschreibung: Background: Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice. Results: After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet. Conclusion: The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.

Beschreibung: Background: Peroxisome proliferator activated receptor alpha (PPARalpha) ameliorates ethanol induced hepatic steatohepatitis. However, its role in alcoholic liver fibrosis has not been fully clarified. The aim of this study was to elucidate the effect and the molecular basis of PPARalpha in ethanol induced liver fibrosis in mice. Methods: C57BL/6J mice were fed with 4% ethanol-containing Lieber-DeCarli liquid diet for eight weeks, and intraperitoneal injected with 5% carbon tetrachloride (CCl4) for the last four weeks to induce alcoholic liver fibrosis. PPARalpha agonist WY14643 was administered to mice during the last couple of weeks. The effects of PPARalpha induction on liver histology, activation of hepatic stellate cells (HSCs), as well as hepatic expression of inflammatory and fibrogenic factors were assessed. Results: The ethanol plus CCl4 treated mice exhibited progressive liver injury including piecemeal necrosis of hepatocytes, severe inflammatory cells infiltration and bridging fibrosis. This was accompanied by down-regulated hepatic expression of PPARalpha and the protective cytokines adiponectin, heme oxygenase-1 and interleukin-10. Additionally, up-regulation of the proinflammatory cytokine tumor necrosis factor-alpha, as well as the profibrogenic genes osteopontin, transforming growth factor-beta 1, visfatin, phosphatidylinositol 3-kinase, matrix metalloproteinase-2 (MMP-2) and MMP-9 was observed. WY14643 treatment restored expression of cytokines altered by ethanol plus CCl4 treatment and concomitantly ameliorated the liver injury. Conclusions: The present study provides evidence for the protective role of PPARalpha induction in ameliorating ethanol mediated fibrosis through mediation of inflammatory and fibrogenic factors.

Beschreibung: Background: Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) is a good marker of cardiovascular risk in adults. It is strongly associated with stroke and many others cardiovascular events. Despite this, the impact of obesity on this enzyme activity and its relation to biomarkers of cardiovascular disease in adolescents is not very well investigated. The purpose of this article is evaluates the influence of obesity and cardiometabolic markers on Lp-PLA2 activity in adolescents. Results: This cross-sectional study included 242 adolescents (10--19 years) of both gender. These subjects were classified in Healthy Weight (n = 77), Overweight (n = 82) and Obese (n = 83) groups. Lipid profile, glucose, insulin, HDL size, LDL(-) and anti-LDL(-) antibodies were analyzed. The Lp-PLA2 activity was determined by a colorimetric commercial kit. Body mass index (BMI), waist circumference and body composition were monitored. Food intake was evaluated using three 24-hour diet recalls. The Lp-PLA2 activity changed in function to high BMI, waist circumference and fat mass percentage. It was also positively associated with HOMA-IR, glucose, insulin and almost all variables of lipid profile. Furthermore, it was negatively related to Apo AI (beta = -0.137; P = 0.038) and strongly positively associated with Apo B (beta = 0.293; P 〈 0.001) and with Apo B/Apo AI ratio (beta = 0.343; P 〈 0.001). The better predictor model for enzyme activity, on multivariate analysis, included Apo B/Apo AI (beta = 0.327; P 〈 0.001), HDL size (beta = -0.326; P 〈 0.001), WC (beta = 0.171; P = 0.006) and glucose (beta = 0.119; P = 0.038). Logistic regression analysis demonstrated that changes in Apo B/Apo AI ratio were associated with a 73.5 times higher risk to elevated Lp-PLA2 activity. Conclusions: Lp-PLA2 changes in function of obesity, and that it shows important associations with markers of cardiovascular risk, in particular with waist circumference, glucose, HDL size and Apo B/Apo AI ratio. These results suggest that Lp-PLA2 activity can be a cardiovascular biomarker in adolescence.

Beschreibung: Background: Phytanic acid (PA) is a chlorophyll metabolite with potentials in regulating glucose metabolism, as it is a natural ligand of the peroxisome proliferator-activated receptor (PPAR) that is known to regulate hepatic glucose homeostasis. This study aimed to establish primary porcine myotubes as a model for measuring glucose uptake and glycogen synthesis, and to examine the impact of physiological amounts of PA on glucose uptake and glycogen synthesis either alone or in combination with insulin. Methods: Porcine satellite cells were cultured into differentiated myotubes and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin. The MIXED procedure model of SAS was used for statistical analysis of data. Results: PA increased glucose uptake by approximately 35%, and the presence of insulin further increased the uptake, but this further increase in uptake was non- additive and less pronounced at high insulin concentrations. There was no effect of PA alone on glycogen synthesis, while the insulin stimulation of glycogen was increased by 20% in the presence of PA. PA neither stimulated glucose uptake nor glycogen synthesis in insulin-resistant myotubes generated by excess glucose exposure. Conclusions: Primary porcine myotubes were established as a model of skeletal muscles for measuring glucose uptake and glycogen synthesis, and we showed that PA can play a role in stimulating glucose uptake at no or inadequate insulin concentrations.

Beschreibung: Background: Microglia are considered the "resident macrophages" of the brain. When in their resting state, microglia perform routine maintenance and immune surveillance. Once activated, either by injury or an immune stimulus, microglia secrete a variety of pro-inflammatory molecules, such as Nitric Oxide, superoxide, and inflammatory cytokines. Up-regulation of pro-inflammatory molecules is transient, and does not cause neurodegeneration. However, if up-regulation lasts for an extended period of time, neurodegeneration ensues.Many neurodegenerative diseases are characterized by chronic inflammation due to microglial activation. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been proposed as possible preventative treatments for neurodegenerative diseases, due to their anti-inflammatory properties. Docosahexaenoic Acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that has potent anti-inflammatory properties.This research work sought to elucidate whether microglial activation can be modulated by combining Aspirin, a classical NSAID, with Docosahexaenoic Acid, a natural anti-inflammatory agent. The combined ability of Aspirin and DHA to modulate microglial activation was determined in the context of pro-inflammatory cytokines, Nitric Oxide levels, as well as total Glutathione levels. Results: Docosahexaenoic Acid increased total Glutathione levels in microglia cells and enhanced their anti-oxidative capacity. It reduced production of the pro-inflammatory cytokines TNF-alpha and IL-6 induced through TLR-3 and TLR-4 activation. Furthermore, it reduced production of Nitric Oxide. Aspirin showed similar anti-inflammatory effects with respect to TNF-alpha during TLR-3 and TLR-7 stimulation. Aspirin did not show any redection in terms of Nitric Oxide production. Combination of Aspirin and Docosahexaenoic Acid showed augmentation in total Glutathione production during TLR-7 stimulation as well as a reduction in IL-6, TNF-alpha and Nitric Oxide. Conclusions: Collectively, these findings highlight the combination of Docosahexaenoic Acid and Aspirin as a possible measure against inflammation of the nervous system, thus leading to protection against neurodegenerative diseases with an inflammatory etiology.

Beschreibung: Background: Sphingosine 1-phosphate (Sph-1-P), abundantly stored in platelets and released extracellularly upon activation, plays important roles as an extracellular mediator by interacting with specific cell surface receptors, especially in the area of vascular biology and immunology/hematology. Although the plasma Sph-1-P level is reportedly determined by red blood cells (RBCs), but not platelets, this may not be true in cases where the platelets have been substantially activated.Methods and results: We measured the Sph-1-P and dihydrosphingosine 1-phosphate (DHSph-1-P) levels in serum samples (in which the platelets had been fully activated) from subjects with (n = 21) and without (n = 33) hematological disorders. We found that patients with essential thrombocythemia exhibited higher serum Sph-1-P and DHSph-1-P concentrations. The serum Sph-1-P concentration was closely correlated with the platelet count but was very weakly correlated with the RBC count. Similar results were obtained for DHSph-1-P. The serum Sph-1-P and DHSph-1-P levels were inversely correlated with the level of autotaxin (ATX), a lysophosphatidic acid-producing enzyme. A multiple regression analysis also revealed that the platelet count had the greatest explanatory impact on the serum Sph-1-P level. Conclusions: Our present results showed close correlations between both the serum Sph-1-P and DHSph-1-P levels and the platelet count (but not the RBC count); these results suggest that high concentrations of these sphingoid base phosphates may be released from platelets and may mediate cross talk between platelet activation and the formation of atherosclerotic lesions.

Beschreibung: Background: Humans and rodents with impaired phytanic acid (PA) metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products. Results: Captive apes and Old world monkeys had significantly higher red blood cell (RBC) PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP) orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates. Conclusions: Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets.

Beschreibung: Background: Atherosclerosis is a postprandial phenomenon. The balanced n-6/n-3 PUFA ratio contributing to the prevention of atherosclerosis has been well shown, but the effect of the ratio on postprandial metabolism has not been fully investigated. The aim of this study was to investigate the effects of the n-6/n-3 PUFAs ratio on postprandial metabolism in hypertriacylglycerolemia patients, comparing them to healthy controls. Methods: Test meals with 0.97 (high n-3) and 8.80 (low n-3) n-6/n-3 PUFAs ratio were administered in a randomized crossover design to 8 healthy and 8 hypertriacylglycerolemia subjects. Blood samples were collected for 8 hours after meals to measure triglyceride (TG), total cholesterol (TC), HDL, ApoA, ApoB, glucose, insulin, inflammatory makers including tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), endothelial function including nitric oxide (NO) and endothelin-1 (ET-1). Results: According to repeated-measures ANOVA, the postprandial response of lipid, glucose, insulin, inflammation and endothelial function were not significantly different between meals. The postprandial TG and NO response were significantly different between healthy control (HC) and hypertriglyceridemia group (HTG) after both meals (P 〈 0.01). After both meals maximal change and iAUC for TG was all higher in HTG group than HC group, the difference was significant after low n-3 meal but not after high n-3 meal. The concentration of glucose, insulin, IL-6, TNFalphaand ET-1 at each time point was higher and NO was lower in HTG group, but the maximal change and iAUC had no significant difference except for iAUC of insulin, IL-6 and diAUC of NO after low n-3 meal. Conclusions: The ratio of n-6 and n-3 maybe do not acutely influence the postprandial metabolism, inflammatory response and endothelial function, but the low n-3 meal can strengthen the difference between HTG and HC group.

Beschreibung: Background: Paraoxonase 1 (PON1) is a cardioprotective, HDL-associated glycoprotein enzyme with broad substrate specificity. Our previous work found associations between dietary cholesterol and vitamin C with PON1 activity. The goal of this study was to determine the effect of specific dietary fatty acid (DFA) intake on PON1 activity. Methods: 1,548 participants with paraoxonase activity measures completed the Harvard Standardized Food Frequency Questionnaire to determine their daily nutrient intake over the past year. Eight saturated, 3 monounsaturated, and 6 polyunsaturated DFAs were measured by the questionnaire. To reduce the number of observations tested, only specific fatty acids that were not highly correlated (r 〈 0.8) with other DFAs or that were representative of other DFAs through high correlation within each respective group (saturated, monounsaturated, or polyunsaturated) were retained for analysis. Six specific DFA intakes - myristic acid (14 carbon atoms, no double bonds - 14:0), oleic acid (18:1), gadoleic acid (20:1), alpha-linolenic acid (18:3), arachidonic acid (20:4), and eicosapentaenoic acid (20:5) - were carried forward to stepwise linear regression, which evaluated the effect of each specific DFA on covariate-adjusted PON1 enzyme activity. Results: Four of the 6 tested DFA intakes - myristic acid (p = 0.038), gadoleic acid (p = 6.68 x 10-7), arachidonic acid (p = 0.0007), and eicosapentaenoic acid (p = 0.013) - were independently associated with covariate-adjusted PON1 enzyme activity. Myristic acid, a saturated fat, and gadoleic acid, a monounsaturated fat, were both positively associated with PON1 activity. Both of the tested polyunsaturated fats, arachidonic acid and eicosapentaenoic acid, were negatively associated with PON1 activity. Conclusions: This study presents the largest cohort-based analysis of the relationship between dietary lipids and PON1 enzyme activity. Further research is necessary to elucidate and understand the specific biological mechanisms, whether direct or regulatory, through which DFAs affect PON1 activity.

Beschreibung: Background: Both L-4 F, one apolipoprotein A-1 mimetic peptide, and statins can reduce progression of atherosclerosis by different mechanisms. The combination of the two drugs can cause lesion regression by rendering HDL anti-inflammatory. We postulated that combination of L-4 F and simvastatin may stimulate cholesterol efflux and related proteins expressions to alleviate atherosclerosis. Methods: Thirty male wild-type (W-T) C57 BL/6 mice and apo E-/- mice were divided into five groups: W-T group, atherosclerosis (AS) group, simvastatin group, L-4 F group and the combination of simvastatin and L-4 F group. After 16 weeks, serum lipids, atherosclerotic lesion areas, cholesterol efflux and the expressions of related proteins including ABCA1, SR-BI, ABCG1, LXRalpha and PPARgamma were evaluated. Results: The aortic atherosclerotic lesion areas were reduced more significantly by combination of both drugs than single agent, and cholesterol efflux was promoted more in combination group than simvastatin and L-4 F group. Besides, the combination group promoted expressions of cholesterol efflux related proteins. Conclusions: The combination of L-4 F and simvastatin reduced atherosclerotic lesions, which stimulates cholesterol efflux by promoting the expressions of related proteins. In addition, these results help us further understand that the regression of the atherosclerosis would be assessed by reduction in LDL-C with increase of cholesterol efflux.

Beschreibung: Background: Majority of studies that focused on the influence of abdominal obesity on lipoprotein profile, were conducted in the fasting conditions. The effects of visceral fat accumulation on postprandial lipoprotein concentrations have not yet been studied in details. We therefore focused on the postprandial lipoprotein profile in otherwise healthy men and women with abdominal obesity and their comparison with the control group of volunteers with normal waist circumference. The concentration of lipoprotein classes and subclasses was measured before and 4 hours after a standard meal by linear polyacrylamide gel electrophoresis. Results: A statistically significant postprandial rise in triacylglycerol concentration occurred in all subjects. VLDL increased 4 hours after meal in all subjects except the women with normal waist circumference. The concentration of large IDL particles increased in both non-obese men and women. In women with abdominal obesity, however, it decreased, while in obese men there was no statistically significant change. The concentration of small and medium-sized IDL particles decreased in all volunteers. Analyzing subclasses changes of large, medium-sized and small LDL particles we saw no significant shift in their concentrations except the subclass of large LDL particles, which decreased in men. Concentrations of medium and small HDL particles decreased postprandially in all volunteers with normal waist circumference. However, they remained unchanged in subjects with abdominal obesity. Conclusions: We observed significant postprandial changes of the lipoprotein profile, but the nature and extent of these changes depended on gender and presence of abdominal obesity.

Beschreibung: AimsHypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses. No second-step strategy is established, however, for cases where strong statins fail to bring cholesterol down to target levels. In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia. Methods: T2DM outpatients (109 patients from 16 institutes) who failed to achieve the target LDL-C value were recruited and randomly assigned to two groups, a double-dose-statin group and ezetimibe-plus-statin group. Follow-ups were scheduled at 0, 12, 26, and 52 weeks. The primary endpoint was the percentage change in the level of LDL-C from baseline to 12 weeks.Interim results: We could successfully create randomized (gender, age, LDL-C, HbA1c, etc.) two groups except for slight differences in apolipoprotein-B and sd-LDL. Conclusions: RESEARCH is the first prospective, parallel-group, multicenter study comparing a double dose of strong statin with ezetimibe plus strong statin for T2DM patients. The RESEARCH study will provide reliable evidence with which to establish a clinical strategy for diabetics who fail to achieve the target LDL-C value.

Beschreibung: Background: There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis alpha (hTNFalpha). Methods: hTNFalpha mice (C57BL/6 hTNFalpha) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. Results: The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of [increment]6 and [increment]9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-gamma level was observed. Plasma carnitine and the carnitine precursor gamma-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal beta-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. Conclusions: The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

Beschreibung: Background: Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain. Methods: Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1--4 weeks, and 14 m/min for 5--8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR. Results: The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect. Conclusions: Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning capacity unlike dietary control.

Beschreibung: Background: Soybean is termed a functional food because it contains bioactive compounds. However, its effects are not well known under unbalanced diet conditions. This work is aimed at evaluating the effect of adding whole soy flour to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity markers in rats. Methods: In this study, 30 male adult Wistar rats were used, distributed among three groups (n = 10): AIN-93 M diet, cafeteria diet (CAF) and cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were measured: food intake; weight gain; serum concentrations of triglycerides, total cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS); humidity and lipid fecal content; weight and fat of the liver. The villous height, the crypt depth and the thickness of the duodenal and ileal circular and longitudinal muscle layers of the animals were also measured. Results: There was a significant reduction in the food intake in the CAF group. The CAFS showed lower serum concentrations of triglycerides and serum TBARS and a lower percentage of hepatic fat, with a corresponding increase in thickness of the intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c and villous height. The addition of soy did not promote any change in these parameters. Conclusions: The inclusion of whole soy flour in a high-fat diet may be helpful in reducing some markers of metabolic risk; however, more studies are required to clarify its effects on unbalanced diets.

Beschreibung: Background: Shark liver oil (SLOil) and fish oil (FOil), which are respectively rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are able to reduce the growth of some tumors and the burden of cachexia. It is known that FOil is able to reduce proliferation rate and increase apoptotic cells and lipid peroxidation of tumor cells efficiently. However, there are few reports revealing the influence of SLOil on these parameters. In the current study, effects of FOil chronic supplementation on tumor growth and cachexia were taken as reference to compare the results obtained with SLOil supplementation. Also, we evaluated if the association of SLOil and FOil was able to promote additive effects. Methods: Weanling male Wistar rats were divided into 4 groups: fed regular chow (C), supplemented (1g/kg body weight) with SLOil (CSLO), FOil (CFO) and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker 256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG composition of tumor and oils were obtained by high performance liquid chromatography and gas chromatography -- mass spectrometry, respectively. Statistical analysis was performed by unpaired t-test and one-way ANOVA followed by a post hoc Tukey test. Results: Fourteen days after inoculation, SLOil was able to restore cachexia parameters to control levels, similarly to FOil. WSLO rats presented significantly lower tumor weight (40%), greater tumor cell apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed more potent effects. Supplementation with SLOil + FOil did not promote additive effects. Additionally, chromatographic results suggested a potential incorporation competition between the n-3 fatty acids and the AKGs in the tumor cells' membranes. Conclusions: SLOil is another marine source of lipids with similar FOil anti-cachectic capacity. Furthermore, despite being less potent than FOil, SLOil presented significant in vivo antitumor effects. These results suggest that the chronic supplementation with SLOil may be adjuvant of the anti-cancer therapy.

Beschreibung: Background: Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist---possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. Methods: Sixteen healthy subjects (8 men; 26.1 +/- 2.5 yrs; 8 women 22.4 +/- 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6--8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. Results: A condition effect was noted for both FFA (p 〈 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p 〉 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p 〈 0.0001), with values higher for supplement compared to placebo. Conclusion: Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.

Beschreibung: Background: Consumption of marine-based oils high in omega-3 polyunsaturated fatty acids (n3PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to protect against obesity-related pathologies. It is less clear whether traditional vegetable oils with high omega-6 polyunsaturated fatty acid (n6PUFA) content exhibit similar therapeutic benefits. As such, this study examined the metabolic effects of a plant-based n3PUFA, stearidonic acid (SDA), in polygenic obese rodents. Methods: Lean (LZR) and obese Zucker (OZR) rats were provided either a standard westernized control diet (CON) with a high n6PUFA to n3PUFA ratio (i.e., 16.2/1.0) or experimental diet modified with flaxseed (FLAX), menhaden (FISH), or SDA oil that resulted in n6PUFA to n3PUFA ratios of 1.7/1.0, 1.3/1.0, and 1.0/0.8, respectively. Results: After 12 weeks, total adiposity, dyslipidemia, glucose intolerance, and hepatic steatosis were all greater, whereas n3PUFA content in liver, adipose, and muscle was lower in OZR vs. LZR rats. Obese rodents fed modified FISH or SDA diets had lower serum lipids and hepatic fat content vs. CON. The omega-3 index (i.e., SigmaEPA + DHA in erythrocyte membrane) was 4.0, 2.4, and 2.0-fold greater in rodents provided FISH, SDA, and FLAX vs. CON diet, irrespective of genotype. Total hepatic n3PUFA and DHA was highest in rats fed FISH, whereas both hepatic and extra-hepatic EPA was higher with FISH and SDA groups. Conclusions: These data indicate that SDA oil represents a viable plant-derived source of n3PUFA, which has therapeutic implications for several obesity-related pathologies.

Beschreibung: Background: 14,15-Epoxyeicosatrienoic acids (14,15-EETs) generated from arachidonic acid by cytochrome P450 epoxygenases have beneficial effects in certain cardiovascular diseases, and increased 14,15-EET levels protect the cardiovascular system. 14,15-EETs are rapidly hydrolyzed by soluble epoxide hydrolase (sEH) to the corresponding 14,15-dihydroxyeicosatrienoic acids (14,15-DHETs), which are generally less biologically active but more stable metabolite. A functionally relevant polymorphism of the CYP2J2 gene is independently associated with an increased risk of coronary heart disease (CHD), and the major CYP2J2 product is 14,15-EETs. 14,15-DHETs can be considered a relevant marker of CYP2J2 activity. Therefore, the aim of the present study was to evaluate the plasma 14,15-DHET levels to reflect the 14,15-EET levels in an indirectly way in patients with CHD, and to highlight the growing body of evidence that 14,15-EETs also play a role in anti-inflammatory and lipid-regulating effects in patients with CHD. This was achieved by investigating the relationship between 14,15-DHETs and high-sensitivity C-reactive protein (hs-CRP) and blood lipoproteins. Methods: Samples of peripheral venous blood were drawn from 60 patients with CHD and 60 healthy controls. A 14,15-DHET enzyme-linked immunosorbent assay kit (14,15-DHET ELISA kit) was used to measure the plasma 14,15-DHET levels. Hs-CRP, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein-cholesterol levels were measured. Results: 14,15-DHET levels (2.53 +/- 1.60 ng/mL) were significantly higher in patients with CHD as compared with those of the healthy controls (1.65 +/- 1.54 ng/mL, P 〈 0.05). There was a significant positive correlation between 14,15-DHETs and hs-CRP levels (R = 0.286, P = 0.027). However, there was no significant correlation between 14,15-DHETs and blood lipoproteins (all, P 〉 0.05). Conclusions: Increased plasma 14,15-DHET levels reflect the decreased of 14,15-EET levels in an indirectly way . Indicated that decreased plasma 14,15-EET levels might be involved in the inflammatory reaction process in atherosclerosis.

Beschreibung: ObjectiveTo study the effects of gamma-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region. Methods: Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed. Results: The rs2592551 polymorphism detection results were 136 cases of wild-type homozygous CC genotype (50.56%), 115 cases of heterozygous CT genotype (42.75%), 18 cases of homozygous TT genotype (6.69%). The allele frequency C was 71.93%, T was 28.07%. The stable warfarin dose average was 2.86 +/- 0.61 mg / d in patients with CC genotype, 3.59 +/- 0.93 mg / d in patients with CT genotype and 4.06 +/- 0.88 mg / d in patients with TT genotype. The warfarin dose in different genotypes were compared, there was statistically significant difference between CC and TT, CC and CT (P 0.05). Conclusion: In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in GGCX gene rs259251 loci required for significantly higher warfarin dose than those with CC genotype. Therefore, rs2592551 polymorphism may one of the factors affecting the warfarin dose in patients with atrial fibrillation.

Beschreibung: ObjectiveNMO and ATM are intertwined both clinically and pathologically. Apolipoprotein (apo) A-I, the main apolipoprotein of HDL, plays an important role in lipid metabolism in the cerebrospinal fluid and is known to suppress pro-inflammatory cytokines generated by activated T cells in some autoimmune diseases as an immune regulator. However, the differences in the levels of serum apoA-I between NMO and ATM patients are unclear. Methods: In the present study, serum apo A-I levels were measured in 53 NMO patients, 45 ATM patients and 49 healthy subjects. We tested serum apoA-I levels in all participants and investigated EDSS scores of patients with NMO and ATM. Statistical analyses were performed by using SPSS statistical software.Result: We found that serum apoA-I levels in patients with NMO were significantly lower in comparison to those with ATM. We also found that serum levels of apoA-I was lower in male subjects in comparison to the female subjects in all groups although these differences were not statistically significant in patients with NMO or ATM. It is also shown in our study that serum apoA-I levels in patients with NMO were significantly elevated after receiving a high dosage of intravenous corticosteroids over a period of one week. However, we did not find any correlation between the apoA-I levels and disease disability. Conclusion: From this study, we concluded that serum levels of apoA-I were lower in NMO patients compared to patients with ATM. Serum apoA-I studies might provide some useful clues to differentiate NMO cases from ATM cases.

Beschreibung: Background: The study of the association between genotype and phenotype is of great importance for the prediction of multiple diseases and pathophysiological conditions. The relationship between angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism and Familial Hypercholesterolemia (FH) has been not fully investigated in all the ethnicities. In this study we sought to determine the frequency of I/D polymorphism genotypes of ACE gene in Saudi patients with FH. Results: This is a case--control study carried out purely in Saudi population. Genomic DNA was isolated from 128 subjects who have participated in this study. ACE gene I/D polymorphism was analyzed by polymerase chain reaction in 64 FH cases and 64 healthy controls. There was no statistically significant difference between the groups with respect to genotype distribution. Furthermore, we did not find any significant difference in the frequency of ACE I/D polymorphism in FH subjects when stratified by gender (p = 0.43). Conclusion: Our data suggest that ACE gene I/D polymorphism examined in this study has no role in predicting the occurrence and diagnosis of FH.

Beschreibung: Background: Due to structural differences, bioavailability of krill oil, a phospholipid based oil, could be higher than fish oil, a triglyceride-based oil, conferring properties that render it more effective than fish oil in increasing omega-3 index and thereby, reducing cardiovascular disease (CVD) risk.ObjectiveThe objective was to assess the effects of krill oil compared with fish oil or a placebo control on plasma and red blood cell (RBC) fatty acid profile in healthy volunteers.Participants and methods: Twenty four healthy volunteers were recruited for a double blinded, randomized, placebo-controlled, crossover trial. The study consisted of three treatment phases including krill or fish oil each providing 600 mg of n-3 polyunsaturated fatty acids (PUFA) or placebo control, corn oil in capsule form. Each treatment lasted 4 wk and was separated by 8 wk washout phases. Results: Krill oil consumption increased plasma (p = 0.0043) and RBC (p = 0.0011) n-3 PUFA concentrations, including EPA and DHA, and reduced n-6:n-3 PUFA ratios (plasma: p = 0.0043, RBC: p = 0.0143) compared with fish oil consumption. Sum of EPA and DHA concentrations in RBC, the omega-3 index, was increased following krill oil supplementation compared with fish oil (p = 0.0143) and control (p 〈 0.0001). Serum triglycerides and HDL cholesterol concentrations did not change with any of the treatments. However, total and LDL cholesterol concentrations were increased following krill (TC: p = 0.0067, LDL: p = 0.0143) and fish oil supplementation (TC: p = 0.0028, LDL: p = 0.0143) compared with control. Conclusions: Consumption of krill oil was well tolerated with no adverse events. Results indicate that krill oil could be more effective than fish oil in increasing n-3 PUFA, reducing n-6:n-3 PUFA ratio, and improving the omega-3 index.Trial registration: clinicaltrials.gov# NCT01323036.

Beschreibung: Background: Adipogenesis from preadipocytes into mature adipocyte is precisely coordinated by transcription factors such as CCAAT-enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARgamma), cytokines, and hormones, which is accompanied by extracellular matrix remodeling. Besides anti-oxidant activity, ascorbic acid (ASC) is participating in collagen biosynthesis and increase production and processing of collagens. Moreover, several studies demonstrated that ASC enhanced differentiation from preadipocytes into mature adipocytes. Methods: The adipogenic effect of ascorbic acid was evaluated in chemical induced 3T3-L1 by Oil Red O staining. This effect was elucidated by immunoblotting which detected the expression level of collagens and transcription factors in adipogenesis. The immunocytochemical determination of type I collagen was performed in 3T3-L1 adipocyte to show the change of extracellular matrix during adipogenesis. Results: In this study, Oil Red O staining in 3T3-L1 preadipocytes was increased dose-dependently by addition of ASC. These ASC-treated adipocytes increased collagen processing of alpha1(I) and alpha1(V) and expressed alpha1(VI) and alpha2(VI) collagens differentially. ASC also stimulated expression of C/EBPalpha and PPARgamma, which is preceded by collagen enhancement. In addition, inhibition of ASC activity by ethyl-3,4-dihydroxybenzoate showed reduction of lipid accumulation by removal of large lipid droplets, not by inhibition of lipid production. This observation went with loss of alpha1(I) deposition on adipocyte surface, increase of alpha1(V) and alpha2(VI) collagens and decrease of C/EBPs. Conclusion: Our findings imply that various actions of ASC on adipogenesis through differential collagen expression may provide diverse applications of ASC to adipose tissue technology.

Beschreibung: Background: Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis. Methods: We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case--control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods. Results: Carriers of the AA and GA + AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003; OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p = 0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study. Conclusions: Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese.

Beschreibung: Background: Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats. Methods: Forty 3-week old male Sprague--Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks. Results: The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain. Conclusions: These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.

Beschreibung: Background: The Daniel Fast involves dietary modification similar to a purified vegan diet. Although improvements in several health-specific biomarkers have been noted with this plan, the removal of animal products results in a significant reduction in both dietary protein and saturated fatty acid intake, which results in a loss of lean body mass and a reduction in HDL-cholesterol. Methods: We assigned 29 men and women to either a traditional or modified Daniel Fast for 21 days and measured anthropometric and biochemical markers of health pre and post intervention. The modified Daniel Fast was otherwise identical to the traditional plan but included one serving per day of lean meat and dairy (skim milk), providing approximately 30 grams per day of additional protein. Results: Compared to baseline, both plans resulted in similar and significant improvements in blood lipids, as well as a reduction in inflammation. Conclusions: Modification of dietary intake in accordance with either a traditional or modified Daniel Fast may improve risk factors for cardiovascular and metabolic disease.

Beschreibung: Background: Early preclinical diagnosis of COPD is urgent. We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases. Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied. It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients. Methods: Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic. The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFalpha, sTNF-RI, bFGF, TGF-beta, IL-8). Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography. Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0. Results: In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established. The amount of the arachidonic acid (20:4n-6) was increased by 13% (p 〈 0.05) in CB patients and by 41% (p 〈 0.001) in COPD patients, as compared with healthy persons. The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased. The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (p 〈 0.05) in CB patients and 2-fold (p 〈 0.001) in COPD patients. The observed increase in the 20:4n-6/20:5n-3 ratio - 1.5-fold (p 〈 0.001) in CB patients and 3-fold in COPD patients - can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development. Conclusions: Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids.

Beschreibung: Background: Serum amyloid A (SAA) is a kind of apolipoprotein. Several studies indicated that SAA genetic polymorphism rs12218 was associated with carotid atherosclerosis, peripheral arterial disease, and serum uric acid levels. However, the relation between rs12218 and lipid levels remains unclear. This study assessed the correlation between SAA1 gene rs12218 polymorphism and lipid levels in a Chinese population. Methods: A total of 823 participants were selected from the subjects for health check in Shanghai Huashan hospital from Jan. 2013 to Mach. 2013. Correlations between rs12218 polymorphism and lipid levels were investigated through the identification of rs12218 genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: We found that the SNP rs12218 was associated with triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels by analyses of a dominant model (P

Beschreibung: During the past 100 years, several theories explaining human atherosclerosis have been postulated and tested. More than anything else, experimental and observational evidence has supported a very strong causal role for dyslipidemia. This has been established as the current paradigm in both biomedical research as well as public health policies. Recently, a novel hypothesis for the etiology of atherosclerosis was presented. The purpose of this commentary is to critically evaluate its validity.

Beschreibung: Background: Ourprevious study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream regionof the beta2 adrenergic receptor gene (ADRB2) issignificantly associated with risk for obesity in Oceanic populations. Methods: To investigate whether the ADRB2 polymorphismsexplain partof the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10ADRB2 SNPs with total-cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceridelevels were examined in 128adults in Tonga. Results: A multiple linear regression analysis adjusted for age, sex, and body mass index revealed thatrs34623097 was significantly associated with triglyceride levels(P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions: In a Tongan population, a SNP located in the upstream region ofADRB2 is associated with triglyceride levels independent of body mass index.

Beschreibung: Background: Over the past two decades, a striking increase in the number of people with metabolic syndrome (MS) has taken place worldwide. With the elevated risk of not only diabetes but also cardiovascular morbidity and mortality, there is urgent need for strategies to prevent this emerging global epidemic. The present study was undertaken to investigate the effects of dietary eicosapentaenoic acid-enriched phospholipid (EPA-PL) on metabolic disorders. Methods: Male C57BL/6J mice (n = 7) were fed one of the following 4 diets for a period of 4 weeks: 1) a modified AIN-96G diet with 5% corn oil (control diet); 2) a high fat (20%, wt/wt) and high fructose (20%, wt/wt) diet (HF diet); 3) the HF diet containing 1% SOY-PL (SOY-PL diet); 4) the HF diet containing 1% EPA-PL (EPA-PL diet). The oral glucose tolerance test was performed. Plasma TG, TC, glucose, NEFA, insulin, leptin, adiponectin, TNF-alpha and IL-6 levels were assessed. In addition, hepatic lipid levels, lipogenic, and lipidolytic enzyme activities and gene expressions were evaluated. Results: Both EPA-PL and SOY-PL significantly inhibited body weight gain and white adipose tissue accumulation, alleviated glucose intolerance, and lowered both serum fasting glucose and NEFA levels substantially. Only EPA-PL significantly reduced serum TNF-alpha and IL-6 levels, and increased serum adiponectin level. EPA-PL was more effective in reducing hepatic and serum TG and TC levels than SOY-PL. Both EPA-PL and SOY-PL reduced the activities of hepatic lipogenic enzymes, such as FAS and G6PDH, but only EPA-PL significantly increased CPT, peroxisomal beta-oxidation enzymes activities and CPT-1a mRNA level. Alterations of hepatic lipogenic gene expressions, such as FAS, G6PDH, ACC, SCD-1 and SREBP-1c were consistent with changes in related enzyme activities. Conclusions: According to our study, EPA-PL supplementation was efficacious in suppressing body fat accumulation, and alleviating insulin resistance and hepatic steatosis by modulating the secretion of adipocytokines and inflammatory cytokines, suppression of SREBP-1c mediated lipogenesis and enhancement of fatty acid beta-oxidation. These results demonstrate that EPA-PL is a novel beneficial food component for the prevention and improvement of metabolic disorders.

Beschreibung: Background: Hypoadiponectinemia in lipoatrophy may be related to worsening of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). One of the beneficial effects of candesartan (Angiotensin II Type 1 receptor blocker) for preventing hypertension may be increasing of adiponectin due to improvement of adipocyte dysfunction. In this study, we determined the effects of candesartan or adiponectin on pathophysiologic features and adipocyte dysfunction in SHRSP. Methods: Candesartan was administered to male SHRSP from 16 to 20 weeks of age (2 mg/kg/day). Adiponectin was cloned and intravenously administered to male SHRSP from 16 to 20 weeks of age. We examined biological parameters, as well as the expression and release of adipokines. Results: The SHRSP exhibited severe atrophy of visceral fat and progression of severe hypertension. The expression and release of leptin and adiponectin were impaired at 6 and 20 weeks of age. Candesartan suppressed the development of lipoatrophy and reduced the incidence of stroke at 20 weeks of age. Candesartan also enhanced the expression of adiponectin and leptin by inducing the overexpression of peroxisome proliferator activated receptor gamma. Circulating level of leptin was significantly higher in candesartan group than in the control group, whereas adiponectin was similar in both groups. Intravenous administration of adiponectin resulted in enhancement of adiponectin expression in adipose tissue, but no remarkable effects were found in pathophysiology in SHRSP. Conclusions: Our results indicate that candesartan protects against hypertension and adipocyte dysfunction in SHRSP. The induction of leptin expression appeared to be important factor in the inhibition of stroke lesions, whereas adiponectin was not a major regulator of blood pressure in SHRSP with genetic hypertension. Further studies are needed to elucidate the role of the renin--angiotensin system in adipose tissue dysfunction in relation to hypertensive end-organ damage.

Beschreibung: Background: Polyunsaturated fatty acids (PUFAs) have positive effect on the regulation of plasma lipids. But the mechanism for them to modulate lipid homeostasis in macrophage is still unclear. In this study, we employed PUFA to pretreat macrophages and evaluated the variations of lipid droplet (LD) content, lipid composition, and expressions of LD-associated genes in macrophage-derived foam cells.MethodTHP-1-derived macrophages or human peripheral blood monocyte-derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs) separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1 macrophage-derived foam cells. Related gene expressions were detected by quantitative real-time PCR. Results: PUFA pre-treatment reduced cholesterol content in foam cells and increased cholesterol efflux to lipid-free apoAI in conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD-associated proteins, showed specific gene expression profiles after PUFA pre-treatment. These results may help to explain the process of lipid metabolism within foam cells. Conclusion: PUFA (LA or EPA) had a potential protective effect against cholesterol accumulation. The specific expressions of CIDE and PAT genes may provide clues to explore the protective mechanism of PUFA in foam cells.

Beschreibung: Background: Studies in animals showed that PCSK9 is involved in HDL metabolism. We investigated the molecular mechanism by which PCSK9 regulates HDL cholesterol concentration and also whether Pcsk9 inactivation might affect cholesterol efflux capacity of serum and atherosclerotic fatty streak volume. Methods: Mass spectrometry and western blot were used to analyze the level of apolipoprotein E (APOE) and A1 (APOA1). A mouse model overexpressing human LDLR was used to test the effect of high levels of liver LDLR on the concentration of HDL cholesterol and APOE-containing HDL subfractions. Pcsk9 knockout males lacking LDLR and APOE were used to test whether LDLR and APOE are necessary for PCSK9-mediated HDL cholesterol regulation. We also investigated the effects of Pcsk9 inactivation on cholesterol efflux capacity of serum using THP-1 and J774.A1 macrophage foam cells and atherosclerotic fatty streak volume in the aortic sinus of Pcsk9 knockout males fed an atherogenic diet. Results: APOE and APOA1 were reduced in the same HDL subfractions of Pcsk9 knockout and human LDLR transgenic male mice. In Pcsk9/Ldlr double-knockout mice, HDL cholesterol concentration was lower than in Ldlr knockout mice and higher than in wild-type controls. In Pcsk9/Apoe double-knockout mice, HDL cholesterol concentration was similar to that of Apoe knockout males. In Pcsk9 knockout males, THP-1 macrophage cholesterol efflux capacity of serum was reduced and the fatty streak lesion volume was similar to wild-type controls. Conclusions: In mice, LDLR and APOE are important factors for PCSK9-mediated HDL regulation. Our data suggest that, although LDLR plays a major role in PCSK9-mediated regulation of HDL cholesterol concentration, it is not the only mechanism and that, regardless of mechanism, APOE is essential. Pcsk9 inactivation decreases the HDL cholesterol concentration and cholesterol efflux capacity in serum, but does not increase atherosclerotic fatty streak volume.

Beschreibung: Background: Conjugated linoleic acids (CLA) in general, and in particular the trans-10,cis-12 (t10,c12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t10,c12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level. Methods: Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c9,t11- and t10,c12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform. Results: Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo-synthesized fatty acids. Total and single trans-octadecenoic acids (e.g., t10-18:1 and t11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans-octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation. Conclusions: Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.

Beschreibung: Diabetes mellitus is a metabolic disease with multiple complications that causes serious diseases over the years. The condition leads to severe economic consequences and is reaching pandemic level globally. Much research is being carried out to address this disease and its underlying molecular mechanism. This review focuses on the diverse role and mechanism of ceramide, a prime sphingolipid signaling molecule, in the pathogenesis of type 1 and type 2 diabetes and its complications. Studies using cultured cells, animal models, and human subjects demonstrate that ceramide is a key player in the induction of beta-cell apoptosis, insulin resistance, and reduction of insulin gene expression. Ceramide induces beta-cell apoptosis by multiple mechanisms namely; activation of extrinsic apoptotic pathway, increasing cytochrome c release, free radical generation, induction of endoplasmic reticulum stress and inhibition of Akt. Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. Better understanding of this area will increase our understanding of the contribution of ceramide to the pathogenesis of diabetes, and further help in identifying potential therapeutic targets for the management of diabetes mellitus and its complications.

Beschreibung: Background: There is considerable interest in dairy products from low-input systems, such as mountain-pasture grazing cows, because these products are believed to be healthier than products from high-input conventional systems. This may be due to a higher content of bioactive components, such as phytanic acid, a PPAR-agonist derived from chlorophyll. However, the effects of such products on human health have been poorly investigated.ObjectiveTo compare the effect of milk-fat from mountain-pasture grazing cows (G) and conventionally fed cows (C) on risk markers of the metabolic syndrome.DesignIn a double-blind, randomized, 12-week, parallel intervention study, 38 healthy subjects replaced part of their habitual dietary fat intake with 39 g fat from test butter made from milk from mountain-pasture grazing cows or from cows fed conventional winter fodder. Glucose-tolerance and circulating risk markers were analysed before and after the intervention. Results: No differences in blood lipids, lipoproteins, hsCRP, insulin, glucose or glucose-tolerance were observed. Interestingly, strong correlations between phytanic acid at baseline and total (P

Beschreibung: Background: Omega-3 PUFAs are known to have anti-inflammatory properties, and different mechanisms are involved. GPR120 is a G-protein coupled receptor that has recently received attention because of its anti-inflammatory signalling properties after binding omega-3 PUFAs. However, both omega-3 and omega-6 PUFAs are natural GPR120 ligands. The aim of this study was to study possible differences in GPR120-mediated signalling events after treatment with different long-chain PUFAs in intestinal epithelial cells. We also investigated possible GPR120-mediated anti-inflammatory effects of different long-chain PUFAs that may be relevant in the understanding of how dietary PUFAs influence inflammatory responses in inflammatory diseases such as IBD. Methods: We used Caco-2 cells as a model system to study GPR120-mediated signalling events because we found this cell line to express GPR120, but not GPR40, another plasma membrane receptor for medium- and long chain fatty acids. Increase in cytosolic Ca2+concentration, activation of MAP kinase ERK1/2 and the inhibition of IL-1beta induced NF-kappaB activity were studied to reveal potential differences in the activation of GPR120 by the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 PUFA arachidonic acid (AA). Results: We found that EPA, DHA and AA enhanced the cytosolic concentration of the second messenger Ca2+ with the same efficiency, but with different kinetics. Both omega-3 and omega-6 PUFAs activated MAP kinase ERK1/2, but differences regarding kinetics and intensity were also observed in this pathway. ERK1/2 activation was shown to be dependent upon EGFR and Raf-1. We further investigated the ability of EPA, DHA and AA to inhibit NF-kappaB activity in Caco-2 cells. All PUFAs tested were able to inhibit IL-1beta induced breakdown of IkappaBalpha after binding to GPR120, but with different potency. Conclusions: Our results show that EPA, DHA and AA elicit the same signalling events, but with different kinetics and efficiency through GPR120 in Caco-2 cells. We show, for the first time, that both omega-3 and omega-6 PUFAs inhibit NF-kappaB activation in intestinal epithelial cells. Our results may be important for understanding how dietary PUFAs influence inflammatory processes relevant in delineating effects of PUFAs in the treatment of IBD.

Beschreibung: Background: The long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have human health benefits. Alternatives to fish as sources of EPA and DHA are needed. Oil from the micro-algae Nannochloropsis oculata contains a significant amount of EPA conjugated to phospholipids and glycolipids and no DHA. Krill oil contains EPA and DHA conjugated to phospholipids. We compare the appearance of fatty acids in blood plasma of healthy humans after consuming a high fat meal followed by either algal oil or krill oil. Methods: Ten healthy males aged 18-45 years consumed a standard high fat (55 g) breakfast followed by either algal oil (providing 1.5 g EPA and no DHA) or krill oil (providing 1.02 g EPA and 0.54 g DHA). All participants consumed both oils in random order and separated by 7 days. Blood samples were collected before the breakfast and at several time points up to 10 hours after taking the oils. Fatty acid concentrations (mug/ml) in plasma were determined by gas chromatography. Results: Fatty acids derived mainly from the breakfast appeared rapidly in plasma, peaking about 3 hours after consuming the breakfast, and in a pattern that reflected their content in the breakfast. There were time-dependent increases in the concentrations of both EPA and DHA with both algal oil (P 〈 0.001 for EPA; P = 0.027 for DHA) and krill oil (P 〈 0.001 for both EPA and DHA). The concentration of EPA was higher with algal oil than with krill oil at several time points. DHA concentration did not differ between oils at any time point. The maximum concentration of EPA was higher with algal oil (P = 0.010) and both the area under the concentration curve (AUC) and the incremental AUC for EPA were greater with algal oil (P = 0.020 and 0.006). There was no difference between oils in the AUC or the incremental AUC for DHA. Conclusion: This study in healthy young men given a single dose of oil indicates that the polar-lipid rich oil from the algae Nannochloropis oculata is a good source of EPA in humans.

Beschreibung: Purpose: This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20 mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg in subgroups of obese (BMI 〉= 30 kg/m2) and non-obese (BMI 〈 30 kg/m2) diabetic subjects. Methods: This was a randomized, double-blind, 12-week study of adults 18--79 years with cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) 〉=70 and

Beschreibung: Background: Pure 1, 3-diacylglycerols (1, 3-DAG) have been considered to be significant surfactants in food, cosmetics and pharmaceutical industries, as well as the effect on obesity prevention. Methods: In this study, a vacuum-driven air bubbling operation mode was developed and evaluated for the enzymatic synthesis of 1, 3-DAG of saturated fatty acids, by direct esterification of glycerol with fatty acids in a solvent-free system. The employed vacuum-driven air bubbling operation mode was comparable to vacuum-driven N2 bubbling protocol, in terms of lauric acid conversion and 1, 3-dilaurin content. Results: Some operation parameters were optimized, and 95.3% of lauric acid conversion and 80.3% of 1, 3-dilaurin content was obtained after 3-h reaction at 50[degree sign]C, with 5 wt% of Lipozyme RM IM (based on reactants) amount. Of the lipases studied, both Lipozyme RM IM and Novozym 435 exhibited good performance in terms of lauric acid conversion. Lipozyme TL IM, however, showed low activity. Lipozyme RM IM showed good operational stability in this operation protocol, 80.2% of the original catalytic activity remained after 10 consecutive batch applications. Some other 1, 3-DAG were prepared and high content was obtained after purification: 98.5% for 1, 3-dicaprylin, 99.2% for 1, 3-dicaprin, 99.1% for 1, 3-dilaurin, 99.5 for 1, 3-dipalmitin and 99.4% for 1, 3-disterin. Conclusion: The established vacuum-driven air bubbling operation protocol had been demonstrated to be a simple-operating, cost-effective, application practical and efficient methodology for 1, 3-DAG preparation.

Beschreibung: Polyunsaturated fatty acids (PUFAs) have tumoricidal action, though the exact mechanism of their action is not clear. The results of the present study showed that of all the fatty acids tested, linoleic acid (LA) and alpha-linolenic acid (ALA) were the most effective in suppressing the growth of normal gastric cells (GES1) at 180 and 200 muM, while gastric carcinoma cells (MGC and SGC) were inhibited at 200 muM. Arachidonic acid (AA) suppressed the growth of GES1, MGC and SGC cells and lower concentrations (120 and 160 muM) of AA were more effective against gastric carcinoma (MGC and SGC) cells compared to normal gastric cells (GES1). Paradoxically, both eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids though are more unsaturated than AA, were less effective compared with LA, ALA and AA in suppressing the growth of both normal and cancer cells. At the concentration used, methotrexate showed much less growth suppressive action compared to all the fatty acids tested. PUFAs-treated cells showed accumulation of lipid droplets. A close association was noted between apoptosis and lipid peroxides formed compared to the ability of normal and tumor cells to generate ROS (reactive oxygen species) and induce SOD (superoxide dismutase activity) in response to fatty acids tested and methotrexate. Both normal and tumor cells generated lipoxin A4 (LXA4) in response to supplementation of fatty acids and methotrexate though no significant correlation was noted between their ability to induce apoptosis and LXA4 formed. These results suggest that PUFAs induced apoptosis of normal gastric and gastric carcinoma cells could, partly, be attributed to lipid peroxidation process.

Beschreibung: Objectives: Variants of the secreted glycoprotein, proprotein convertase subtilisin/kexin 9 (PCSK9), associate with both hypo- and hyper-cholesterolemic phenotypes. Herein, we carried out full exonic sequencing of PCSK9 documenting the frequency of single and multiple PCSK9 variations and their effects on serum lipoprotein and PCSK9 levels in Caucasian Canadians. Methods: The 12 exons of PCSK9 were sequenced in 207 unrelated Caucasian Canadians. Minor allele frequencies of PCSK9 variants were compared amongst LDL cholesterol (LDLC) quintiles. Serum PCSK9 levels were measured by ELISA and lipoproteins by enzymatic methods. Comparisons were made with a Caucasian family cohort (n = 51) and first generation African Canadians (n = 31). Results: In Caucasians, but not African Canadians, the c.61_63insCTG (denoted L10Ins) and A53V PCSK9 variations were linked and their frequency was significantly higher among Caucasian Canadians with LDLC levels in the

Beschreibung: Background: Previous studies have reported that different genotypes of PTPN11 gene (protein tyrosine phosphatase, non-receptor 11) were associated with different levels of serum lipids. The aim of this study was to explore the relationship between single nucleotide polymorphisms (SNPs) of PTPN11 and serum lipids in Northeast Chinese. Methods: A total of 1003 subjects, 584 males and 419 females, were included in the study and their serum lipids were determined. Five htSNPs (rs2301756, rs12423190, rs12229892, rs7958372 and rs4767860) of PTPN11 gene were genotyped using TaqMan assay method. Results: All of the five SNPs were in Hardy-Weinberg equilibrium. The male subjects had higher triglyceride (TG), higher low-density lipoprotein cholesterol (LDL-C) and lower high-density lipoprotein cholesterol (HDL-C) level than females. In males, rs4767860 was found to be associated with serum TG and total cholesterol (TC) levels and rs12229892 was associated with TC level. However, these significant associations could not be observed in females. In females, rs2301756 was found to be associated with TG and rs7958372 was associated with LDL-C level. Haplotype analysis showed that the GCGTG haplotype was associated with slightly higher TG level and ATGCG with higher TC level. Conclusions: SNPs of PTPN11 may play a role in serum lipids in a sex-specific pattern. However, more studies are needed to confirm the conclusion and explore the underlying mechanism.

Beschreibung: Background: During postprandial state, TG concentration is increasing and HDL cholesterol decreasing, leading to a transitory pro-atherosclerotic profile. Previous studies have reported that bicarbonate water improve postprandial lipemia. The objective of this study was to analyze the effect of a strongly bicarbonated mineral water on lipoprotein levels during fasting and postprandial state. Methods: A controlled, randomised, double-blind cross-over design was conducted in 12 moderately hypercholesterolemic subjects after a daily ingestion of 1.25 L of mineral (SY) or low mineral water during eight weeks separated by a one week wash-out period. Blood samples were collected in first visit to the hospital (V1) before water consumption (referent or SY) and in a second visit (V2) after eight week water consumption period. The effect of the consumed water was studied in fasting and in postprandial state during ingestion of a meal and 0.5 L of water. Results: No difference was observed between SY and referent water consumption for measured parameters at fasting and postprandial state. Comparison of data between V1 and V2 after SY consumption showed a significant decrease in triglyceridemia (23%), VLDL TG(31%) and tendency to a decrease of VLDL cholesterol (p = 0.066) at fasting state. Whatever the consumed water during postprandial state, the measurement of total areas under curves did not show a significant difference. Conclusion: Although this study did not show any difference between the two waters, we showed a decrease of basal TG and VLDLTG when subjects consumed SY. In discussion section, we discussed the unexpected absence of effect of high mineralized water on postprandial lipemia.

Beschreibung: Background: It is now established that patients with hyperlipidemia have a high risk of atherosclerosis and thrombotic complications, which are two important events responsible for the onset and progression of cardiovascular disease. In the context of managing dyslipidemia by means of dietary advice based on the consumption of argan oil, we wanted to investigate the effect of virgin argan oil on plasma lipids, and for the first time, on the platelet hyperactivation and oxidative status associated with dyslipidemia. This study concerns patients recruited in the area of Rabat in Morocco. Methods: 39 dyslipidemic (79% women) patients were recruited for our study in the area of Rabat in Morocco. They were randomly assigned to the two following groups: the argan group, in which the subjects consumed 25 mL/day of argan oil at breakfast for 3 weeks, and the control group in which argan oil was replaced by butter. Results: After a 3-week consumption period, blood total cholesterol was significantly lower in the argan oil group, as was LDL cholesterol (23.8% and 25.6% lower, respectively). However, the HDL cholesterol level had increased by 26% at the end of the intervention period compared to baseline. Interestingly, in the argan oil group thrombin-induced platelet aggregation was lower, and oxidative status was enhanced as a result of lower platelet MDA and higher GPx activity, respectively. Conclusions: In conclusion, our results, even if it is not representative of the Moroccan population, show that argan oil can prevent the prothrombotic complications associated with dyslipidemia, which are a major risk factor for cardiovascular disease.

Beschreibung: Background: Many health effects of oils rich in oleic acid (18:1 n9) seem to be opposite those of arachidonic acid (20:4 n6), i.e. concerning cardiovascular risk. In recent study in rats we observed that percentages of oleic acid and arachidonic acid were inversely related in total serum lipids. In the present work we investigate whether an inverse relationship between this couple of fatty acids also exists in the phospholipid fraction of human sera. Methods: The study group consisted of 11 men and 35 women. Mean age was 23.8 +/- 2.5 years (mean +/- SD), and the body mass index was 23.5 +/- 3.2 kg/m2. After fasting overnight, blood was drawn and the concentration of fatty acids in serum phospholipids was determined, using gas chromatography. We studied the association between percentages of oleic acid and arachidonic acid using bivariate correlations (Pearson), and multiple linear regressions. Results: We found an inverse relationship (r = -0.563, p 〈 0.001; n = 46) between % oleic acid and % arachidonic acid in the serum phosholipid fraction of the 46 fasting subjects. By multiple linear regression, and % 20:4 n6 as the dependent variable, the inverse association with % 18:1 n9 persisted when controlling for sex, age, body mass index, and percentages of the other fatty acids measured (t = -17.6, p 〈 0.001). Per cent 20:4 n6 seemed to correlate negatively (r = -0.289, p = 0.05) with the (18:1 n9)/(18:0) ratio, estimating Delta9 desaturase activity, and % oleic acid correlated negatively (r = -0.321, p = 0.029) with the (20:4)/(18:2) ratio, estimating desaturases/elongase activities. Conclusions: In a group of healthy human subjects, percentages of oleic acid and arachidonic acid were inversely related, and the inverse association persisted when controlling for possible confounding variables. The findings might contribute to explain positive health effects of foods rich in oleic acid.

Beschreibung: Background: Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid (LCPUFA) that is critically important for the structure, development and function of the retina and central nervous system (CNS), ultimately contributing to improved cognition. It is known that the DHA content of breast milk is positively correlated with maternal DHA intake. Since there is a lack of information about the DHA status of pregnant and lactating women in rural Taiwan. The aims of the present study were to: 1) assess the DHA status of mothers and babies in urban setting, and 2) determine the content of DHA in the milk of nursing mothers. Methods: All pregnant women who attended the Obstetrics and Gynecology Outpatient Clinic of Kinmen Hospital on Kinmen Island in Taiwan between May 1 and May 30, 2011 were invited by research nurses to enroll in the study. The maternal blood sample was obtained on the day of their delivery. Cord blood was collected by the obstetrician following delivery. Participants were asked to visit the doctor forty-two days after the delivery, at which time a nurse collected breast milk on the day mothers were visiting the doctor for post-natal well-baby check-up. Results: The DHA percentages of maternal and neonatal plasma phospholipids were 5.16% and 6.36%, respectively, which are higher than values reported for most populations elsewhere in the world. The DHA percentage for the breast milk of Kinmen mothers was also high (0.98%) relation to international norms. The DHA proportions in maternal and neonatal plasma phospholipids were positively correlated (r = 0.46, p = 0.01). Conclusions: We show that the DHA status of mothers and newborns on Kinmen Island is satisfactory, thereby providing an evidence-based argument for promoting breastfeeding in Taiwan.

Beschreibung: Intake of high-fat diet is associated with increased fatty livers. Hepatic lipid accumulation and oxidative stress are key pathophysiological mechanisms in this disease. Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to hepatoprotection, but most of these micronutrients are removed by the traditional refining process. The purpose of the present study was to determine whether rapeseed oil fortified with these micronutrients can decrease hepatic lipid accumulation and oxidative stress induced by high-fat diet. Sprague--Dawley rats received rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified RRO with low, middle and high quantities of these micronutrients for 10 weeks. Intake of RRO caused a remarkable hepatic steatosis. Micronutrients supplementation was effective in reducing steatosis as well as total triglyceride and total cholesterol contents in liver. These micronutrients also significantly increased hepatic antioxidant defense capacities, as evaluated by the significant elevation in the activities of SOD and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. These findings suggest that rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent fatty livers such as nonalcoholic fatty liver disease by ameliorating hepatic lipid accumulation and oxidative stress.

Beschreibung: Background: Our previous work showed that dietary oxidized linoleic acid given, as a single fatty acid, to LDL receptor knockout mice decreased weight gain as compared to control mice. Other studies have also reported that animals fed oils heated for 24 h or greater showed reduced weight gain. These observations, while important, have limited significance since fried foods in the typical human diet do not contain the extreme levels of oxidized lipids used in these studies. The main goal of this study was to investigate the effects of a diet containing soybean oil heated for 3 h on weight gain and fat pad mass in mice. Additionally, because PPARgamma and UCP-1 mediate adipocyte differentiation and thermogenesis, respectively, the effect of this diet on these proteins was also examined.FindingsFour to six week old male C57BL/6 J mice were randomly divided into three groups and given either a low fat diet with heated soybean oil (HSO) or unheated soybean oil (USO) or pair fed for 16 weeks. Weight and food intake were monitored and fat pads were harvested upon the study's termination. Mice consuming the HSO diet had significantly increased fat pad mass but gained less weight as compared to mice in the USO group despite a similar caloric intake and similar levels of PPARgamma and UCP1. Conclusion: This is the first study to show that a diet containing soybean oil heated for a short time increases fat mass despite a decreased weight gain in C57BL/6 J mice. The subsequent metabolic consequences of this increased fat mass merits further investigation.

Beschreibung: Background: Lipid desaturase enzymes mediate the metabolism of fatty acids to long chain polyunsaturated fatty acids and their activities are related to metabolic risk factors for Type 2 diabetes (T2DM) and coronary heart disease (CHD). There are marked ethnic differences in risks of CHD and T2DM but little is known about ethnic differences in desaturase activities. Methods: Samples from a study of CVD risk in women with previous gestational diabetes were analysed for percentage fatty acids in plasma free fatty acid, triglyceride, cholesterol ester and phospholipid pools for 89 white European, 53 African Caribbean and 56 Asian Indian women. The fatty acid desaturase activities, stearoyl-CoA desaturase (SCD, calculated separately for C16 and C18 fatty acids), delta 6 desaturase (D6D) and delta 5 desaturase (D5D) were estimated from precursor-to-product ratios and their relationships with adiposity, blood pressure, cholesterol, triglycerides, HDL cholesterol and insulin sensitivity explored. Ethnic differences in desaturase activities independent of ethnic variation in risk factor correlates of desaturase activities were then identified. Results: There was significant ethnic variation in age, BMI, waist circumference, blood pressure, serum triglycerides and HDL cholesterol concentrations and insulin resistance. Desaturase activities showed significant correlations, independent of ethnicity, with BMI, waist circumference, triglycerides and HDL cholesterol. Independent of ethnic variation in BMI, waist circumference, triglycerides and HDL cholesterol, SCD-16 activity, calculated from each of the four lipid pools measured, was 18--35 percent higher in white Europeans than in African Caribbeans or Asian Indians (all p 〈 0.001). Similar, though less consistent differences were apparent for SCD-18 activity. Also independently of risk factor variation, but specifically when calculated from the cholesterol ester and phospholipid, pools, D6D activity was significantly lower in Asian Indians, and D5D activity higher in African Caribbeans. Conclusions: Significant ethnic differences exist in desaturase activities, independently of ethnic variation in other risk factors. These characteristics did not accord with higher risk of T2DM among African Caribbeans and Asian Indians nor with lower risk of CHD among African Caribbeans but did accord with the higher risk of CHD in Asian Indians.

Beschreibung: Background: Obesity, oxidative stress and inflammation, by triggering insulin resistance, may contribute to the accumulation of hepatic fat, and this accumulation by lipotoxicity can lead the organ to fail. Because obesity is growing at an alarming rate and, worryingly, in a precocious way, the present study aimed to investigate the effects of moderate physical training performed from childhood to adulthood on liver fat metabolism in rats. Methods: Twenty rats that were 28 days old were divided into two groups: control (C) and trained (T). The C Group was kept in cages without exercise, and the T group was submitted to swimming exercise for 1 hour/day, 5 days/week from 28 to 90 days of age (8 weeks) at 80% of the anaerobic threshold determined by the lactate minimum test. At the end of the experiment, the body weight gain, insulin sensitivity (glucose disappearance rate during the insulin tolerance test), concentrations of free fatty acids (FFA) and triglycerides (TG) and hepatic lipogenic rate were analyzed. For the statistical analysis, the Student t-test was used with the level of significance preset at 5%. Results: The T group showed lower body weight gain, FFA concentrations, fat accumulation, hepatic lipogenic rate and insulin resistance. Conclusion: The regular practice of moderate physical exercise from childhood can contribute to the reduction of obesity and insulin resistance and help prevent the development of accumulation of hepatic fat in adulthood.

Beschreibung: Background: The aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM). Methods: Serum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11--22) ) and high-molecular-weight (HMW( number of KIV repeats: 〉22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: =20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period. Results: During the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P 〈 0.01, 3.621; 95% CI, 1.50-8.75; P 〈 0.05, and 7.15; 95% CI, 2.17-23.56; P 〈 0.01, respectively). Conclusions: Our results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.

Beschreibung: A PPARgamma fluorescence polarization (FP) assay was used to measure the release of fatty acid products from triglyceride emulsions during digestion with pancreatic and yeast lipases in a real-time, homogenous assay. Using the same FP assay we show the anti-obesity drug Orlistat is a PPARgamma ligand with an IC50 of 2.84 +/- 0.16 muM. Analytical Mass Spectrometry confirms that Orlistat does not bind covalently to PPARgamma. The PPARgamma FP assay is shown to be a simple method for measuring real-time lipase activity using a number of triglyceride substrates including olive oil and grape seed oil emulsions. Incubation of Orlistat with the human intestinal epithelial cell line Caco-2, at concentrations of 1 - 100 muM, leads to induction of genes regulated by PPARgamma. At 100 muM Orlistat, transcription of beta-defensin 1 (hDB1) & Adipose Differentiation Related Protein (ADRP) increase by up to 2.6 fold and 6.8 fold, respectively. Although at 1 muM and 100 muM Orlistat did not significantly increase defensin protein synthesis, at 10 muM Orlistat induced a 1.5 fold increase in hDB1 protein secretion in the human colonic adenocarcinoma cell line HT-29. Thus Orlistat is similar to the anti-diabetic drug Rosiglitazone in its ability to induce defensin gene expression. The antimicrobial peptide beta-defensin 1 protects against pathogenic micro-organisms in the gut and PPARgamma suppresses inflammatory gene expression. These may be beneficial side effects of Orlistat consumption on gut epithelial cells.

Beschreibung: Background: We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM). Methods: We included 68 DCM patients with left ventricular ejection fraction (LVEF)

Beschreibung: Background: Maize-based food is typical in Mexico and other Mesoamerican countries. Used for millennia, they have recently been replaced by modern food that is associated with an increase in the prevalence of non-communicable chronic diseases. This study was carried out in order to evaluate the effects of traditional food on lipid profiles. Methods: Metabolic syndrome was induced in animals given a 30% sucrose solution. The animals were given maize tortillas (n=5) and maize pozol (n=5), traditional Mexican food items. A control group was given a 30% sucrose solution in the laboratory diet (n=5) and a witness group was given plain water and pellets. Triglycerides, cholesterol and glucose in tail blood were recorded each month between weeks 12 to 24. Blood was obtained from the cardiac cavity on week 28 and triglycerides, total cholesterol, LDL, HDL, C-reactive protein, alanine amino transferase, glucose and glycated hemoglobin were recorded. Results: The animals provided with supplementary traditional food presented a lower increase in triglycerides up to week 24 (p

Beschreibung: Background: B-Cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Clinical treatment of CLL is often limited due to drug resistance and severe therapy-induced toxicities. We hypothesized that the omega 3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), would increase the sensitivity of malignant B-lymphocytes to anti-cancer drugs doxorubicin, vincristine and/or fludarabine in vitro and that increased sensitivity is achieved by alterations in cell-cycle progression leading to growth inhibition and/or enhanced cell death. We further postulate that enhanced sensitivity is dependent on the formation of lipid peroxides and to the generation of reactive oxygen species (ROS). Methods: In the present study, B-CLL-derived leukemic cell lines EHEB and MEC-2 and the B-Prolymphocytic leukemic-derived (PLL) cell line JVM-2 were tested for in vitro sensitivity against doxorubicin, vincristine or fludarabine in the presence or absence of vehicle, arachidonic acid (omega 6), EPA or DHA. Cell cycle analysis and Annexin-V assays were performed to determine cell cycle progression and% apoptotic cells, respectively. Assays for malondialdehyde, a measure of lipid peroxidation, and DCF fluorescence assays, a measure of intracellular ROS, were performed to determine if enhanced sensitivity of cells to the drugs by n-3 was dependent on the formation of ROS. Results: Our results indicated that: 1) EPA and DHA differentially sensitized B-leukemic cell lines EHEB, JVM-2 and MEC-2 to doxorubicin, vincristine and fludarabine in vitro; 2) n-3 alone and with drug treatment increased cell death and induced G2/M arrest in a cell-type specific manner; 3) lipid peroxidation increased in the presence of n-3; 4) there was higher lipid peroxidation in MEC-2 cells in presence of DHA and doxorubicin than with either alone; 5) n-3 increased generation of ROS in MEC-2, and 6) the addition of vitamin-E abrogated the increase in ROS generation and chemo-sensitivity of MEC-2 to doxorubicin by DHA. Conclusion: N-3's are promising chemo-sensitizing agents for the treatment of CLL. Selective enhancement of chemo-sensitivity of EHEB, JVM-2 and MEC-2 to drugs by n-3 that is not dependent on increased lipid peroxidation and ROS generation indicates alternative mechanisms by which n-3 enhances chemo-sensitivity.

Beschreibung: Background: Epidemiological studies have shown that the offspring of mothers who experience diabetes mellitus during pregnancy are seven times more likely to develop health complications than the offspring of mothers who do not suffer from diabetes during pregnancy. The present study was designed to investigate whether supplementation of streptozotocin (STZ)-induced diabetic pregnant mice with thymoquinone (TQ) during pregnancy and lactation improves the risk of developing diabetic complications acquired by their offspring. Methods: Three groups of pregnant female mice were used: non-diabetic control dams (CD), diabetic dams (DD), and diabetic dams supplemented with TQ (DD + TQ) during pregnancy and lactation (n = 10 female mice in each group). Results: Our data demonstrated a marked decrease in the number of neonates born to DD, and these neonates showed a marked increase in their mean body weight (macrosomic pups) compared to those born to CD and DD + TQ. The induction of diabetes during pregnancy and lactation resulted in macrosomic pups with several postpartum complications, such as a marked increase in their levels of blood glucose, free radicals, plasma pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and lipids, and a tendency toward abnormal obesity compared to the offspring of CD. By contrast, macrosomic offspring born to DD exhibited a marked reduction in plasma cytokine levels (IL-2, -4 and -7), an obvious reduction in the number of circulating lymphocytes, decreased proliferation of superantigen (SEB)-stimulated lymphocytes and aberrant AKT phosphorylation. Interestingly, the supplementation of DD with TQ during pregnancy and lactation had an obvious and significant effect on the number and mean body weight of neonates. Furthermore, TQ significantly restored the levels of blood glucose, insulin, free radicals, plasma cytokines, and lipids as well as lymphocyte proliferation in the offspring. Conclusions: Our data suggest that the nutritional supplementation of DD with the natural antioxidant TQ during pregnancy and lactation protects their offspring from developing diabetic complications and preserves an efficient lymphocyte immune response later in life.

Beschreibung: Background: In an effort to identify new alternatives for long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplementation, the effect of three sources of omega 3 fatty acids (algae, fish and Echium oils) on lipid profile and inflammation biomarkers was evaluated in LDL receptor knockout mice. Methods: The animals received a high fat diet and were supplemented by gavage with an emulsion containing water (CON), docosahexaenoic acid (DHA, 42.89%) from algae oil (ALG), eicosapentaenoic acid (EPA, 19.97%) plus DHA (11.51%) from fish oil (FIS), and alpha-linolenic acid (ALA, 26.75%) plus stearidonic acid (SDA, 11.13%) from Echium oil (ECH) for 4 weeks. Results: Animals supplemented with Echium oil presented lower cholesterol total and triacylglycerol concentrations than control group (CON) and lower VLDL than all of the other groups, constituting the best lipoprotein profile observed in our study. Moreover, the Echium oil attenuated the hepatic steatosis caused by the high fat diet. However, in contrast to the marine oils, Echium oil did not affect the levels of transcription factors involved in lipid metabolism, such as Peroxisome Proliferator Activated Receptor alpha (PPAR alpha) and Liver X Receptor alpha (LXR alpha), suggesting that it exerts its beneficial effects by a mechanism other than those observed to EPA and DHA. Echium oil also reduced N-6/N-3 FA ratio in hepatic tissue, which can have been responsible for the attenuation of steatosis hepatic observed in ECH group. None of the supplemented oils reduced the inflammation biomarkers. Conclusion: Our results suggest that Echium oil represents an alternative as natural ingredient to be applied in functional foods to reduce cardiovascular disease risk factors.

Beschreibung: Background: Women often lag behind men in their risk of cardiovascular events. However, with age and the onset of menopause, women's cardiovascular risk eventually becomes similar to that of men. This change in risk may, in part, be attributable to a shift to a more atherogenic lipid profile. Our objective was to evaluate standard- and sub-lipid parameters and the apo A1 remnant ratio: (apo A1/[VLDL3-C+IDL-C]) for their associations with death/myocardial infarction among peri- and post-menopausal women. Methods: Women (N=711) 〉50 years of age undergoing coronary angiography were evaluated. Baseline clinical and angiographic characteristics, lipids, and sub-lipid levels (Vertical Auto Profile method) were collected. Cox regression analysis, adjusted by standard cardiovascular risk factors, was utilized to determine associations of lipid and sub-lipid tertiles(T) with death/myocardial infarction at 1 and 3 years. Results: Patients averaged 67.7+/-9.4 years and 53.6% had underlying severe (〉=70% stenosis) coronary artery disease. The apo A1 remnant ratio was found to have stronger associations for 1 year (T1 vs. T3: HR=2.13, p=0.03, T2 vs. T3: HR=1.57, p=0.21) and 3 year (T1 vs. T3: HR=2.32, p=0.002, T2 vs. T3: HR=1.97, p=0.01) death/myocardial infarction than any individual lipid (LDL-C, HDL-C, triglycerides, non-HDL-C) or sub-lipid (apo A1, apo B, VLDL3-C+IDL-C) measure, or any other well-known ratio (triglyercies/HDL-C, apo B/A1, TChol/HDL-C, HDL-C/[VLDL3-C+IDL-C]). Conclusions: The apo A1 remnant ratio was a significant predictor of short and intermediate-term death/myocardial infarction risk among women 〉50 years of age. Furthermore, this ratio was found to have greater predictive ability than traditional lipid and sub-lipid parameters and represents a potential new risk marker.

Beschreibung: Background: Growth hormone (GH) and insulin signaling pathways are known important regulators of adipose homeostasis. The cross-talk between GH and insulin signaling pathways in mature adipocytes is poorly understood. Methods: In the present study, the impact of insulin on GH-mediated signaling in differentiated 3T3-F442A adipocytes and primary mice adipocytes was examined. Results: Insulin alone did not induce STAT5 tyrosine phosphorylation, but enhanced GH-induced STAT5 activation. This effect was more pronounced when insulin was added 20 min prior to GH treatment. The above results were further confirmed by in vivo study, showing that insulin pretreatment potentiated GH- induced STAT5 tyrosine phosphorylation in visceral adipose tissues of C57/BL6 mice. In addition, our in vitro results showed that IGF-I had similar potentiating effect as insulin on GH-induced STAT5 activation. In vitro, insulin and IGF-I had an additive effect on GH- induced MAPK activation. Conclusion: These results indicate that both insulin and IGF-I specifically potentiated GH mediated STAT5 activation in mature adipose cells. These findings suggest that insulin and GH, usually with antagonistic functions, might act synergistically to regulate some specific functions in mature adipocytes.

Beschreibung: Background: Intake of high-fat diet is associated with increased non-alcoholic fatty liver disease (NAFLD). Hepatic lipid accumulation and oxidative stress are key pathophysiological mechanisms in NAFLD. Both flaxseed oil (FO) and alpha-lipoic acid (LA) exert potential benefit to NAFLD. The aim of this study was to determine the effect of the combination of FO and LA on hepatic lipid accumulation and oxidative stress in rats induced by high-fat diet. Methods: LA was dissolved in flaxseed oil to a final concentration of 8 g/kg (FO + LA). The rodent diet contained 20% fat. One-fifth of the fat was soybean oil and the others were lard (control group), or 75% lard and 25% FO + LA (L-FO + LA group), or 50% lard and 50% FO + LA (M-FO + LA group), or FO + LA (H-FO + LA group). Male Sprague--Dawley rats were fed for 10 weeks and then killed for liver collection. Results: Intake of high-fat lard caused a significant hepatic steatosis. Replacement with FO + LA was effective in reducing steatosis as well as total triglyceride and total cholesterol contents in liver. The combination of FO and LA also significantly elevated hepatic antioxidant defense capacities, as evaluated by the remarkable increase in the activities of SOD, CAT and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. Conclusion: The combination of FO and LA may contribute to prevent fatty livers such as NAFLD by ameliorating hepatic lipid accumulation and oxidative stress.

Beschreibung: Background: Previously, we demonstrated that trans fatty acid ingestion during pregnancy and lactation caused a pro-inflammatory effect on the newborn. The opposite effect was described for gestational prebiotic intake. In the present study, we examined whether supplementation of the diet of the dams with 10% of oligofructose with or without hydrogenated vegetable fat affected the pro-inflammatory status during pregnancy and lactation on the pups at age 21 days. Methods: On the first day of pregnancy, rats were divided into four groups, each of which received one of four diets: a control diet (C group), a control diet supplemented with 10% oligofructose (CF group), a diet enriched with hydrogenated vegetable fat containing trans fatty acids (T group) or a diet enriched with hydrogenated vegetable fat containing trans fatty acids supplemented with 10% oligofructose (TF group). The pups were weighed at birth and at 7, 14 and 21 days of life and were euthanized on post-natal day 21. The serum glucose, insulin and adiponectin concentrations were analyzed. The IL-6, IL-10 and TNF-alpha contents of the retroperitoneal white adipose tissue, liver, soleus and extensor digital longus muscles were analyzed by ELISA. The results are presented as the means +/- standard error of the mean. Statistical significance was assessed using two-way ANOVA, followed by Tukey's test and considered significant at p 〈 0.05 Results: The body weights of the 21-day old pups in the CF and TF groups were significant lower than those of the C (27% and 21%) and T (25% and 19%, respectively) groups. The serum levels of adiponectin in the CF, T and TF groups were lower than in the C group (41%; 34% and 31%, respectively). In the retroperitoneal adipose tissue, the IL-6 content was increased in TF group relative to the C and CF groups (74% for both), and the TNF-alpha content was higher in the T and TF groups than in the C group (62% and 98%, respectively). In the liver, the TNF-alpha (56% and 104%) and IL-10 (52% and 73%) contents were increased in the CF group relative to the C and TF groups. Conclusions: Supplementation of the diet of the dams with 10% of oligofructose during pregnancy and lactation, independent of supplementation with hydrogenated vegetable fat, adversely affected the development of the offspring and contributed to development of a pro-inflammatory status in the pups on postnatal day 21.

Beschreibung: Background: Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the reproduction of male animals are widely described in the literature. However, there is little information about the effect of n-3/n-6 ratios on male health and reproduction. The aim of this study was to investigate the effects of diets with different omega-3/omega-6 polyunsaturated fatty acid (n-3/n-6 PUFA) ratios on the reproductive performance of male rats. Methods: Eighty male Sprague Dawley (SD) rats were supplemented with diets containing different n-3/n-6 PUFA ratios (0.13, 0.40, 0.85, 1.52 and 2.85) for 60 days. Half of the rats in each group were sacrificed on day 60, and the other half were chosen to mate with female mice to assess the effects of n-3/n-6 ratios on reproductive performance. Results: Sperm density and sperm motility of the 1.52 group were higher than other groups (P 〈 .05), and the development of testis and the morphological structure of sperm in the 1.52 group were better than other groups. Furthermore, a higher litter size and birth weights of offspring were observed in the 1.52 group. Additionally, serum reproductive hormone levels were significantly affected by the n-3/n-6 ratios. Conclusion: These findings demonstrated that a balanced n-3/n-6 ratio was important in male rat reproduction. Therefore there is a necessity to determine an appropriate n-3/n-6 PUFA ratio in man and different male animals in the future.

Beschreibung: Background: Betaine is a methyl donor and has been considered a lipotropic effect substance. But its mechanism remains unclear. Hepatic steatosis is associated with abnormal expression of genes involved in hepatic lipid metabolism. DNA methylation contributes to the disregulation of gene expression. Here we hypothesized that betaine supplement and subsequent DNA methylation modifications alter the expression of genes that are involved in hepatic lipid metabolism and hence alleviate hepatic triglyceride accumulation. Methods: Male wild-type (WT) C57BL/6 mice (n = 6) were fed with the AIN-93 G diet. ApoE-/- mice (n = 12), weight-matched with the WT mice, were divided into two groups (n = 6 per group), and fed with the AIN-93 G diet and AIN-93 G supplemented with 2% betaine/100 g diet. Seven weeks after the intervention, mice were sacrificed. Liver betaine, choline, homocysteine concentration were measured by HPLC. Liver oxidants activity and triglyceride level were assessed by ultraviolet spectrophotometry. Finally, hepatic PPAR alpha gene and its target gene expression levels and the methylation status of the PPAR alpha gene were determined. Results: ApoE-/- mice had higher hepatic triglyceride and lower GSH-Px activity when compared with the WT mice. Betaine intervention reversed triglyceride deposit, enhanced SOD and GSH-Px activity in the liver. Interestingly, mice fed on betaine-supplemented diet showed a dramatic increase of hepatic choline concentration and a decrease of betaine and homocysteine concentration relative to the WT mice and the ApoE-/- mice absent with betaine intervention. Expression of PPAR alpha and CPT1 were decreased and expression of FAS was markedly increased in ApoE-/- mice. In parallel, PPAR alpha promoter methylation level were slightly decreased in ApoE-/- mice though without significance. Betaine supplement upregulated expression of PPAR alpha and its target genes (CPT1, CYP2E1) and reversed hypermethylation of PPAR alpha promoter of ApoE-/- mice. Furthermore, PPAR alpha methylation was positively correlated with hepatic betaine concentration. Conclusions: Our findings indicate that betaine supplement could alleviate hepatic triglyceride accumulation and improve antioxidant capacity by decreasing PPAR alpha promoter methylation and upregulating PPAR alpha and its target genes mRNA expression.

Beschreibung: Background: Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. Methods: Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Results: Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions. CETP protein level and activity was significantly increased while apoB levels were significantly decreased following insulin analog initiation therapy. No significant difference was found in LCAT mass, LCAT activity, apoA-I and PON-1 arylesterase levels following insulin initiation therapy. Conclusion: These findings indicate that insulin analog initiation therapy activates lipid metabolism via up-regulating CETP and shows anti-atherogenic effects by increasing HDL-large and decreasing LDL-3 and LDL-4 subfractions in a short time period.

Beschreibung: Background: Adults born preterm at very low birth weight (VLBW

Beschreibung: Keloids are common cutaneous pathological scars that are characterised by the histological accumulation of fibroblasts, collagen fibres, and clinically significant invasive growth. Although increasing lines of research on keloids have revealed genetic and environmental factors that contribute to their formation, the etiology of these scars remains unclear. Several studies have suggested the involvement of lipid metabolism, from a nutritional point of view. However, the role that lipid metabolism plays in the pathogenesis and progression of keloids has not previously been reviewed. The progress that has been made in understanding the roles of the pro- and anti-inflammatory lipid mediators in inflammation, and how they relate to the formation and progression of keloids, is also outlined. In particular, the possible relationships between mechanotransduction and lipid metabolites in keloids are explored. Mechanotransduction is the process by which physical forces are converted into biochemical signals that are then integrated into cellular responses. It is possible that lipid rafts and caveolae provide the location of lipid signaling and interactions between these signaling pathways and mechanotransduction. Moreover, interactions between lipid signaling pathway molecules and mechanotransduction molecules have been observed. A better understanding of the lipid profile changes and the functional roles lipid metabolism plays in keloids will help to identify target molecules for the development of novel interventions that can prevent, reduce, or even reverse pathological scar formation and/or progression.

Beschreibung: Background: Prevalence of metabolic syndrome is high and increasing in China. The causation of this disorder is, yet, to be fully understood. Several studies with confirmatory factor analysis have been performed to investigate the core of the disease in some races other than Chinese, and amongst the other studies, they have yielded a sound model fit. This study was to evaluate and compare two single-factor models of the underlying factor structure of metabolic syndrome in a Chinese population using confirmatory factor analysis. Results: Findings showed that in a Chinese sample of 7,472 individuals, Model 1 (with waist circumference, triglycerides/HDL-C ratio, fasting plasma glucose and mean artery pressure) yielded good level of fitness (SRMR 〈 0.08, CFI 〉 0.96 and RMSEA 〈 0.10) in men and women of all age groups; and Model 2 (with waist circumference, triglycerides, fasting plasma glucose and systolic blood pressure) fitted well in men aged 18--34 and over 60 and in all women, except in men of 35--59 (RMSEA = 0.142). In comparison, Model 2 were shown to be better fit (with relative larger GFI and smaller AIC, BIC, CAIC, and EVIC) in women of all age groups and in men of 18--34 and over 60 years old; Model 1 had a better fit in men between 35 and 59. Conclusions: This study suggests that the single-factor model of metabolic syndrome with waist circumference, triglycerides, fasting plasma glucose and systolic blood pressure are plausible in women of all age groups and young and senior men in Beijing. The model with waist circumference, triglycerides/HDL-C ratio, fasting plasma glucose and mean artery pressure fits middle-aged men.

Beschreibung: Dietary polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), improve lipid metabolism and contribute to the prevention of vascular diseases such as atherosclerosis. However, EPA in the diet is easily oxidized at room temperature and several types of oxidized EPA (OEPA) derivatives are generated. To compare the efficiencies of OEPAs on lipid metabolism with EPA, human hepatocellular liver carcinoma cell line (HepG2) was treated with EPA or OEPAs and their effects on lipid metabolism related genes were studied. OEPAs more potently suppressed the expression of sterol-responsive element-binding protein (SREBP)-1c, a major transcription factor that activates the expression of lipogenic genes, and its downstream target genes than did EPA under conditions of lipid synthesis enhanced by T0901317, a synthetic liver X receptor (LXR) agonist. Furthermore, PGC-1beta, a coactivator of both LXRalpha and SREBP-1, was markedly down-regulated by OEPAs compared with EPA. The treatment of OEPAs also significantly down-regulated the expression of glycerol-3-phosphate acyltransferase (GPA), the initiating enzyme in triacylglycerol (TG) synthesis, more than EPA. Therefore, the advantageous effects of OEPAs on cardiovascular diseases might be due to their SREBP-1c, PGC-1beta and GPA mediated ameliorating effects.

Beschreibung: We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5 +/- 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome.

Beschreibung: Background: People who skip breakfast have more visceral fat than those who eat breakfast; however, the mechanism underlying this difference is unclear. In this study, we examined 3 T3-L1 adipocytes and assessed 1) whether restricted feeding (i.e., "breakfast skipping") alters the cyclic expression of BMAL1 (brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) and lipogenic proteins and 2) whether repeated exposure to growth media at the time-points with enhanced lipogenic regulatory signals increases de novo lipogenesis and lipid storage. Methods: Differentiated adipocytes were divided into two groups: a control group and a restricted feeding group, for which incubation with growth medium from ZT 9 to ZT 12 was withheld. Results: A bout of restricted feeding disrupted the cyclic expression of BMAL1 protein and increased the expression of lipogenic proteins, such as fatty acid synthase and peroxisome proliferator-activated receptor gamma in adipocytes. Furthermore, the repeated exposure to growth media at the time-points with enhanced lipogenic regulatory signals increased de novo lipogenesis and lipid storage. Conclusion: These findings suggest that direct disruption of intracellular molecular clock systems by breakfast skipping and the concurrent changes in the daily cycle of lipogenic proteins in adipocytes, as a consequence of repeated nutrition at the time-points with enhanced lipogenic regulatory signals, would result in increased lipogenesis and lipid storage. These alterations are important molecular mechanisms underlying augmented adiposity induced by breakfast skipping.

Beschreibung: Background: The excessive accumulation of body fat is a major risk factor to develop a variety of metabolic diseases. To investigate the systematic association between the differences in gene expression profiling and adipose deposition, we used pig as a model, and measured the gene expression profiling of six variant adipose tissues in male and females from three pig breeds which display distinct fat level. Results: We identified various differential expressed genes among breeds, tissues and between sexes, and further used a clustering method to identify sets of functionally co-expression genes linked to different obesity-related phenotypes. Our results reveal that the subcutaneous adipose tissues mainly modulate metabolic indicators, nonetheless, the visceral adipose tissues as well as the intermuscular adipose tissue were mainly associated with the impaired inflammatory and immune response. Conclusions: The present study provided the evidence of gene expression profiling that the subcutaneous adipose tissues are mainly affected the metabolism process, whereas the visceral and intermuscular adipose tissues should been term as the metabolic risk factors of obesity.

Beschreibung: Background: In recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores. Methods: The present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships. Results: A significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045). Conclusions: These findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations.

Beschreibung: Background: Elevated total plasma homocysteine (tHcy) in humans is associated with cardiovascular disease but prevention trials have failed to confirm causality. Reported reasons for this association have been that homocysteine and its major genetic determinant methylenetetrahydrofolate reductase (MTHFR) may have an effect on HDL and Apolipoprotein (Apo) A1 levels. We wanted to study if tHcy and its major determinants were correlated with Apo A1 levels in a large population without folate fortification. Methods: This study was a prospective incident nested case-referent study within the Northern Sweden Health and Disease Study Cohort (NSHDSC), including 545 cases with first myocardial infarction and 1054 matched referents, median age at inclusion was 59 years. Univariate and multiple regression analyzes was used to study the associations between apolipoproteins Apo A1 and B, tHcy, folate and vitamin B12 in plasma as well as MTHFR polymorphisms 677C〉T and 1298A〉C. Results: Apo A1 and Apo B were strongly associated with the risk of a first myocardial infarction. tHcy was not associated with Apo A1 levels. Instead, folate had an independent positive association with Apo A1 levels in univariate and multiple regression models. The associations were seen in all men and women, among referents but not among cases. MTHFR polymorphisms had no clear effect on Apo A1 levels. Conclusions: Analyzing over 1500 subjects we found an independent positive association between plasma folate (major dietary determinant of tHcy) and Apo A1 levels among those who later did not develop a first myocardial infarction. No association was seen between tHcy and Apo A1.

Beschreibung: Background: Serum low-density lipoprotein cholesterol (LDL-C) is one of the most important risk factors for coronary heart disease. The aim of the present study was to investigate the relationship between LDL-C and body mass index (BMI) in population-based Japanese schoolchildren. Methods: The subjects comprised all fourth graders and seventh graders in Ina Town, Saitama Prefecture, Japan, during 2002-2009. Information about each subject's age, sex, and family history of hypercholesterolemia was collected using a self-administered questionnaire. The body height, weight, and LDL-C were measured for each child. LDL-C was measured using the direct method. According to the LDL-C criteria of the Japan Atherosclerosis Society, LDL-C level was categorized into three subgroups: acceptable, 〈 110 mg/dL; borderline, 110-139 mg/dL; and high, 〉= 140 mg/dL. Children with either borderline or high LDL-C level were considered to have high-normal LDL-C (HLDL-C). Results: Data from a total of 5869 subjects were analyzed. A higher BMI category was associated with a higher prevalence of HLDL-C regardless of sex or grade level (P 〈 0.05). When compared with the

Beschreibung: Background: Nigella sativa belonging to the Ranunculaceae family has been reported to use for thousands of years as protective and curative traditional medicine against a number of diseases. GC-MS analysis of methanolic extract (ME) and volatile oil (VO) extracted from Nigella sativa seed oil was performed by two different mass spectrometry libraries, WIlEY8 and NIST05s. The cholesterol lowering and antioxidant actions of VO and ME fractions were investigated in atherogenic suspension fed rats. Methods: In this study, four groups of male Wistar rats were used: normolipidemic control (NLP-C), hyperlipidemic control (HLP-C), methanolic extract (HLP-ME) and volatile oil treated (HLP-VO) groups for 30 days of duration. P value 〈 0.05 was assumed as significant data in groups. Results: Administration of atherogenic suspension to male Wistar rats for 30 days resulted in a marked increase of plasma triglycerides and total cholesterol, and significant change in plasma lipoprotein levels along with a decrease in antioxidant arylesterase activity in hyperlipidemic control (HLP-C) group. The oral feeding of 100 mg ME or 20 mg VO per rat/day effectively reduced the plasma triglycerides to near normal level, while high density lipoprotein cholesterol and its subfraction along with arylesterase activity levels were significantly increased. The test fractions elicited a significant decrease in hepatic HMG-CoA reductase activity. The fractions significantly blocked the ex vivo basal and in vitro maximal formation of conjugated diene and malondialdehyde, and lengthened the lag times of low density lipoprotein, small dense low density lipoprotein and large buoyant low density lipoprotein. ME possessing omega-6 linoleic acid along with palmitic acid active compounds was more effective than VO extract containing thymol and isothymol phenolic antioxidant compounds, thymoquinone phenolic compound common to the both extracts, via reduction in hepatic HMG-CoA reductase activity as well as antioxidant mechanisms. Conclusion: The both extracts especially, ME significantly improve cardiovascular risk parameters in treated rats, and can be used in reactive oxygen species disorders such as cardiovascular diseases.

Beschreibung: Background: We have previously demonstrated that increased rates of superoxide generation by extra-mitochondrial enzymes induce the activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) in the livers of hypertriglyceridemic (HTG) mice. The resulting mild uncoupling mediated by mitoKATP protects mitochondria against oxidative damage. In this study, we investigate whether immune cells from HTG mice also present increased mitoKATP activity and evaluate the influence of this trait on cell redox state and viability. Methods: Oxygen consumption (Clark-type electrode), reactive oxygen species production (dihydroethidium and H2-DCF-DA probes) and cell death (annexin V, cytocrome c release and Trypan blue exclusion) were determined in spleen mononuclear cells Results: HTG mice mononuclear cells displayed increased mitoKATP activity, as evidenced by higher resting respiration rates that were sensitive to mitoKATP antagonists. Whole cell superoxide production and apoptosis rates were increased in HTG cells. Inhibition of mitoKATP further increased the production of reactive oxygen species and apoptosis in these cells. Incubation with HTG serum induced apoptosis more strongly in WT cells than in HTG mononuclear cells. Cytochrome c release into the cytosol and caspase 8 activity were both increased in HTG cells, indicating that cell death signaling starts upstream of the mitochondria but does involve this organelle. Accordingly, a reduced number of blood circulating lymphocytes was found in HTG mice. Conclusions: These results demonstrate that spleen mononuclear cells from hyperlipidemic mice have more active mitoKATP channels, which downregulate mitochondrial superoxide generation. The increased apoptosis rate observed in these cells is exacerbated by closing the mitoKATP channels. Thus, mitoKATP opening acts as a protective mechanism that reduces cell death induced by hyperlipidemia.