Deoxycholic acid ameliorates obesity and insulin resistance by enhancing lipolysis and thermogenesis

Background: Bile acids are essential for energy metabolism. Deoxycholic acid (DCA) in particular is associated with metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity. However, the direct effects of DCA on metabolism and body composition have yet to be studied in depth. Methods: Targeted metabolomics analysis of human feces was performed. C57BL/6J mice fed a high-fat diet (HFD) were gavaged with DCA, and the effects were measured by metabolic tolerance tests and metabolic cages. Body composition was evaluated by echoMRI. To evaluate the beneficial function of DCA on thermogenesis and lipolysis, histological staining and qPCR were carried out. Results: There was negative correlation between fecal DCA levels and serum glucose levels, as well as the Homeostatic Model Assessment for Insulin Resistance (HOMA) index in humans. Our findings confirmed that DCA could ameliorate glucose metabolism and insulin sensitivity in mice fed with HFD. DCA supplementation alleviated HFD-induced obesity and decreased the fat mass significantly by promoting lipolysis. Moreover, DCA significantly enhanced energy expenditure and thermogenesis in brown adipose tissue in mice with obesity induced by HFD. Conclusions: Based on the results of our mouse model, DCA may have applications in alleviating obesity and its related metabolic disorders in humans.