ALBERT

Description: Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC–MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut–liver axis health.

Description: About 20–30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE−1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE−1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet−induced obesity (DIO) and leptin−deficient (ob/ob) mice. PaPE−1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE−1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE−1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE−1 and suggest that PaPE−1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.