The gut microbiota-derived metabolite indole-3-propionic acid enhances leptin sensitivity by targeting STAT3 against diet-induced obesity.

ABSTRACT: Obesity is associated with the gut microbiome. Here, we report that gut commensal Clostridia bacteria regulate host energy balance through the tryptophan-derived metabolite indole-3-propionic acid (IPA). IPA acts as an endogenous leptin sensitiser to counteract obesity. Mechanistically, IPA is secreted from the gut into the circulation, and then targets to the STAT3 in the hypothalamic appetite regulation centre, promoting its phosphorylation and nuclear translocation, which enhances the body's response to leptin, and regulates the balance between appetite and energy metabolism. The in vitro pull-down assays involving site-directed mutagenesis demonstrate that Trp623 in the SH2 domain is the key binding site for STAT3-IPA interaction. High-fat diet (HFD), rather than genetic factors, induc

SUBMITTER: Wang Z 

PROVIDER: S-EPMC11602751 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature