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  • 1
    ISSN: 1573-4919
    Keywords: Zucker rat ; amino acid metabolism ; skeletal muscle ; obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Measurements of the tissue accumulation of α-amino[1-14C]isobutyrate [1-14C]AIB) in lean (+/?) and obese (fa/fa) Zucker rats showed an augmented tissue/plasma ratio in the liver of the obese animals. In contrast, brown adipose tissue AIB accumulation was lower in the fa/fa animals. In response to a 24h starvation period AIB accumulation was significantly elevated in the liver and plasma of the lean animals and was unchanged in the liver of the fa/fa animals. The circulating concentration of alanine and branched-chain amino acids was elevated in the fa/fa animals as compared to their lean counterparts. These observations suggest that amino acid uptake is not involved in the impaired muscle development observed in the obese Zucker rat and that the ability of brown adipose tissue for amino acid utilization is decreased in the obese animals suggesting that this may partially explain the impaired thermoregulatory capacity observed in brown adipose tissue of obese Zucker rats.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 112 (1992), S. 53-59 
    ISSN: 1573-4919
    Keywords: tumour necrosis factor-α ; glucose ; intestine ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Intravenous administration of a single dose (20 μg) of recombinant tumour necrosis factor-α (TNF, cachectin) to rats decreased the rate of intestinal glucose absorption. In vivo, the oxidation of [U-14C]glucose to 14CO2 was significantly increased by the cytokine. In addition, [14C]lipid accumulation from [U-14C]glucose was increased both in liver and brown adipose tissue of the TNF-injected animals. The decrease observed in intestinal glucose absorption was not associated with changes in intestinal metabolism. There was no difference in glucose metabolism by isolated enterocytes from either control or TNF-injected rats whether in the absence or presence of different concentrations of the cytokine in the incubation medium. In contrast, tumour necrosis factor altered the rate of gastric emptying as measured by the gastrointestinal distribution of [3H]inulin following an intragastric glucose load. These results suggest that the cytokine profoundly alters glucose metabolism by increasing its whole-body oxidation rate and delaying intestinal absorption through a reduced gastric emptying.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 81 (1988), S. 3-17 
    ISSN: 1573-4919
    Keywords: cancer ; tumor metabolism ; host's metabolism ; energetic efficiency ; futile cycling ; energy imbalance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The tumor cell has a very distinctive metabolism. It acts as a metabolic trap for host nutrients thus taking vital compounds for the metabolism of the host. Depending on the particular tumor growing pattern, cancer cells use preferentially glucose or amino acids for their energetic or biosynthetic needs. Lipids, fatty acids in particular, can also be taken up by the tumor cell. In addition, it can also release some compounds into the host circulation which are not normally produced by the original cell before neoplastic transformation. Some of these compounds affect the metabolism of the host in an unfavorable way since they can oppose the host's metabolic responses, which sustain homeostasis. The final product is that the metabolic machinery of these cells allows them to grow continuously in an uncontrolled manner. The consequences of tumor invasion on the host's metabolism are varied. They have, however, one thing in common: the reduction of the metabolic efficiency of the host. Muscular protein depletion, increased gluconeogenesis, uncoupling of oxidative phosphorylation constitute the main metabolic responses of the host as a result of tumor invasion. The net result of all these metabolic changes is profound energy imbalance which normally ends with cachexia and, eventually, death.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 143 (1995), S. 113-118 
    ISSN: 1573-4919
    Keywords: brown adipose tissue ; tumour necrosis factor ; thermogenesis ; glucose metabolism ; lipid metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Intravenous administration of a single dose (100 μg/kg bw) of recombinant tumour necrosis factor-α (TNF, cachectin) to rats increased the rate ofin vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 165 (1996), S. 17-23 
    ISSN: 1573-4919
    Keywords: tumour ; lipid metabolism ; lipoprotein lipase ; lipogenesis ; cachexia ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rats bearing the Yoshida AH-130 ascites hepatoma showed important changes in lipid metabolism. The presence of this rapidly growing tumour induced a significant reduction in the intestinal absorption of an oral [l4C]triolein load but without changes in whole body oxidation of the tracer to CO3. Both white (WAT) and brown (BAT) adipose tissue lipoprotein lipase (LPL) activities were increased at day 4 of tumour growth, changes that seem to be related with those observed in [14C] lipid accumulation; however, heart LPL activity was increased at day 7 but there was no change at day 4. In addition, there was a marked hyperlipemia in the tumour-bearing animals, whereas the blood ketone body concentrations were lower in these animals in comparison with the corresponding pair-fed group. The in vivo lipogenic rate was increased in liver of the tumour-bearing animals (day 4); conversely, it was decreased in WAT and skeletal muscle (day 4) and IBAT (day 7) of the AH-130-bearing rats. It may be suggested that the increased liver lipogenic rate associated with tumour burden is the main factor contributing to the hyperlipidaemia present in the Yoshida AH-130 bearing rats.
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  • 6
    ISSN: 1573-4919
    Keywords: lipogenesis ; intestine ; spleen ; phrase ; refeeding ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Intraperitoneal administration of [1,2-14C]-acetate to Wistar rats was used to assess tissue lipogenic rates after estimating the incorporation of the label into the tissular lipid fractions. Refeeding the animals with glucose (after an overnight fast) induced an increase in white adipose tissue (4.5 fold), liver (4.1 fold), small intestine (1.9 fold), carcass (2.9 fold) and spleen (3.7 fold) lipogenesis (expressed as the radioactivity present in the lipid fraction corrected by the plasma circulating radioactivity). No changes were found following refeeding in either brain or brown adipose tissue. Administration of mannoheptulose (an inhibitor of insulin secretion) to refed rats completely abolished the increased lipogenesis in white adipose tissue, liver, carcass, spleen and small intestine, thus suggesting that insulin secretion is involved in this phenomenon. This is the first report showing that spleen lipogenesis may be modulated by refeeding via insulin secretion and suggests an important role of this organ on the in vivo lipogenic response of the organism after carbohydrate refeeding. (Mol Cell Biochem 175: 149–152, 1997)
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  • 7
    ISSN: 1573-4919
    Keywords: lipopolysaccharide ; tumour necrosis factor-α cachexia ; leucine oxidation ; interleukin-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Septic rats (as induced by cecal puncture and ligation) showed an increased rate ofin vivo leucine oxidation as measured from the formation of14CO2 from an intravenously injected [1-14C]leucine tracer dose. Acute lipopolysaccharide (LPS) administration (1 mg/kg) to rats caused a similar effect on the rate ofin vivo leucine oxidation. Additionally, both tumour necrosis factor-α (TNF) and interleukin-1-α (IL-1), in an acute dose of 100 μg/kg, also increased the rate of the oxidation of the amino acid, although only IL-1 caused a similar increase to that observed following LPS. The observed increased leucine oxidation was related to lower leucine concentrations both in LPS- and cytokine-treated rats. Important decreases were also observed in the other branched-chain amino acids (valine and isoleucine) in the LPS- and IL-1-treated animals. Isolated incubated muscles from TNF- and IL-1-treated rats did not show any changes in the rate of leucine utilization, thus suggesting that the mechanism by which the cytokines stimulate whole-body leucine oxidation is not based on an increase in the activity of the enzymatic machinery responsible for leucine oxidation. Additionally, glucocorticoids do not seem to mediate the enhancedin vivo oxidation of the amino acid since, although they are increased by both LPS and cytokines, treatment of the animals with RU486 (a glucocorticoid antagonist) was not able to suppress the effects of the cytokine onin vivo leucine oxidation.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 148 (1995), S. 17-23 
    ISSN: 1573-4919
    Keywords: muscle wasting ; tumour growth ; TNF ; protein metabolism ; amino acids ; caquexia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Rats bearing the Yoshida AH-130 ascites hepatoma show decreased activity of neutral amino acid transport in skeletal muscle measuredin vivo as the tissue accumulation of the analogue α-amino [1-14C]isobutyrate (AIB). The decreased accumulation of AIB observed is not merely a consequence of the hypoinsulinaemia present in these animals (as a result of tumour burden) sincein vitro experiments carried out using incubations of isolated soleus muscles also showed a decreased uptake of neutral amino acids. In these preparations the addition of insulin results in similar increases in uptake both in the pair-fed controls and the tumour-bearing animals, thus suggesting similar insulin sensitivities. The decrease in amino acid uptake in soleus muscle is associated with a decrease in the activity of system A, while systems L and ASC show no particular changes as a result of the tumour growth. The kinetic characterisation of system A in the Yoshida-bearing rats shows a decrease in Vmax together with a decrease in KM in relation with the pair-fed animals.
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  • 9
    ISSN: 1573-4919
    Keywords: tumor necrosis factor ; cytokines ; protein metabolism ; skeletal muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Acute treatment of rats with recombinant tumour necrosis factor (TNF-α) caused an enhanced proteolytic rate —measured as tyrosine released in the presence of cycloheximide — insoleus muscle (34%). The cytokine treatment also decreased the rate of protein synthesis in this muscle (22%) while it had no effect upon the same parameter inextensor digitorum longus (EDL) (26%) muscle. In addition, treatment of rats with TNF-α increased amino acid uptake by transport system A in the incubated muscles both insoleus (45%) andEDL (99%) in the presence of insulin in the incubating medium. This effect was not associated with a direct action of TNF on muscle since the addition of different concentrations of the cytokine to the preparations did not alter the uptake of α-(methyl)-aminoisobutyric acid by the incubated muscles. It can be concluded that acute TNF-α treatment causes changes in protein metabolism in red-type muscles — suchsoleus — while little effects are seen in white-type muscles — such as EDL. The results presented may, to some extent, be related to the cachectic response associated with cancer and inflammation.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Bioscience reports 11 (1991), S. 285-292 
    ISSN: 1573-4935
    Keywords: glucose ; hepatocytes ; obese rat ; Zucker rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Hepatocytes isolated from obese Zucker rats showed a significantly higher rate of both [U-14C]glucose and [U-14C]lactate incorporation into [14C]lipid than those from their lean counterparts. This was associated with a marked increase in the lipogenic rate measured by the incorporation of3H2O into the cell esterified fatty acids. Although there were no changes in the incorporation of the tracer into either [14C]glycogen or14CO2, the [14C] total uptake was significantly higher in the obese animals. The high rate of [14C]lipid synthesis from glucose was observed both at 15 and 30 mM substrate concentrations and was linked to an enhanced uptake of the tracer into the cell as measured using the decarboxilation of [1-14C]glucose in the presence of phenazine methosulphate. The presence of insulin in the incubation medium had no effect on the uptake of glucose by the liver cells. However, the large uptake of glucose by the hepatocytes from the obese animals was not related to an enhanced rate of transport as measured using 3-O-methyl[U-14C]glucose. The activity of glucose-6-phosphate dehydrogenase together with a higher [1-14C]glucose/[U-14C]glucose descarboxylation ratio indicate a predominant very active pentose phosphate pathway which may be responsible for the enhanced glucose uptake observed in the hepatocytes from the obese animals.
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