Bazedoxifene and conjugated estrogen combination maintains metabolic homeostasis and benefits liver health

The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to characterize the effects of various estrogens on liver. The CE+BZA combination was very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet (HFD). In CE+BZA treated animals, liver weight and hepatic lipid deposition were significantly lower than in Vehicle (Veh) treated animals. Additionally, CE+BZA induced unique liver transcriptome and plasma metabolome profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Blood plasma metabolite analysis identified several metabolites similar to and distinct from other estrogen treatments. Integrated pathway analysis showed that gene networks that were associated with inflammation, reactive oxygen species pathway and lipid metabolism and their relevant metabolites were regulated significantly by CE+BZA treatment. Thus, long-term CE+BZA treatment modulated hepatic metabolic gene networks and their associated metabolites and improves hepatic health without stimulating the uterus. PMID:29267318

Estrogens and female liver health

Due to declining estrogen levels during menopause, NAFLD prevalence is higher in postmenopausal women compared to in premenopausal women or in men. Postmenopausal women are more susceptible to weight gain, fat redistribution and dyslipidemia, all major hallmarks of metabolic syndrome associated with increased NAFLD risk. Gut microbiota plays important roles in development of gastrointestinal tract, metabolism and immunity. Host-microbe interactions allows regulation of a wide range of pathways that affect healthy and diseased physiology. Recent advances in – omics technologies, such as microbiome, transcriptome and metabolome analysis, provided evidence that estrogens and intestinal microbiota (IM) can collectively influence obesity, inflammatory disease, diabetes, and cancers. By understanding underlying mechanisms of estrogens and microbiota crosstalk, we might design dietary and pharmacological interventions to alleviate the metabolic syndrome and NAFLD. PMID:29100781