The incidence of nonalcoholic fatty liver disease (NAFLD) in postmenopausal women has increased significantly. Estrogen plays a very important role in NAFLD, but whether NAFLD in premenopausal women was caused by estrogen deficiency was unknown. Thus, it is of great clinical significance to explore the mechanism of NAFLD in premenopausal women. Gut microbiota and its metabolites short chain fatty acids (SCFA) have been shown to play important roles in the development of NAFLD. In this study, we investigated the impact of gut microbiota and SCFA in NAFLD patients and mice caused by estrogen deficiency. We showed that premenopause NAFLD patients had much lower estrogen levels. Estrogen deficient mice, due to ovariectomy (OVX), suffered more severe liver steatosis with an elevated body weight, abdominal fat weight, serum triglycerides and deterioration in hepatic steatosis. Altered gut microbiota composition and decreased butyrate content were found in NAFLD patients and in OVX mice. Furthermore, fecal microbiota transplantation (FMT) or supplementing with butyrate alleviated NAFLD in OVX mice. The production of antimicrobial peptides (AMP) Reg3ɣ, β-defensins and the expression of intestinal epithelial tight junction, including ZO-1 and Occluding-5, were decreased in the OVX mice compared to control mice. Upregulation of PPAR-ɣ and VLDLR, downregulation of PPAR-ɑ indicated that OVX mice suffered from abnormal lipid metabolism. These data indicate that changes in the gut microbiota and SCFA caused by estrogen reduction, together with a disorder in AMP production and lipid metabolism, promote NAFLD, thus provide SCFAs derived from microbiota as new therapeutic targets for the clinical prevention and treatment of NAFLD.

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The higher prevalence of metabolic syndrome (MetS) in women after menopause is associated with a decrease in circulating 17β-oestradiol. To explore novel treatments for MetS in women with oestrogen deficiency, we studied the effect of exogenous butyrate on diet-induced obesity and metabolic dysfunctions using ovariectomized (OVX) mice as a menopause model. Oral administration of sodium butyrate (NaB) reduced the body fat content and blood lipids, increased whole-body energy expenditure, and improved insulin sensitivity. Additionally, NaB induced oestrogen receptor alpha (ERα) expression, activated the phosphorylation of AMPK and PGC1α, and improved mitochondrial aerobic respiration in cultured skeletal muscle cells. In conclusion, oral NaB improves metabolic parameters in OVX mice with diet-induced obesity. Oral supplementation with NaB might provide a novel therapeutic approach to treating MetS in women with menopause. Graphical Abstract

Objective Triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio is correlated with metabolic diseases. The prevalence of sarcopenia is significantly higher in type 2 diabetes mellitus (T2DM) patients compared with healthy controls. The purpose of our study is to evaluate the correlation of TG/HDL-C ratio with muscle mass in T2DM patients. Method Our study consists of 1048 T2DM inpatients recruited from the department of endocrinology. Skeletal muscle index (SMI) was detected with a dual energy X-ray absorptiometry method. Low muscle mass was diagnosed using the criteria of SMI less than 7.0 kg/m2 (in male subjects) or 5.4 kg/m2 (in female subjects). Result The prevalence of low muscle mass was 20.9% and 14.5% in male and female groups respectively. SMI was correlated with TG/HDL ratio after adjustment for age, duration of diabetes, diastolic blood pressure (DBP), and HbA1c in male subgroup. In female subgroup, SMI was associated with TG/HDL ratio after adjustment for age and DBP. Conclusion Higher TG/HDL-C ratio is correlated with muscle mass in T2DM patients.