Butyrate mitigates metabolic dysfunctions via the ERα-AMPK pathway in muscle in OVX mice with diet-induced obesity

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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01119-y.