Endocrine Abstracts

Bariatric surgery, also known as metabolic surgery, has been shown through multiple clinical trials to result in superior efficacy and sustainability of weight loss and remission of diabetes after surgery in patients with extreme obesity compared with intensive medical and lifestyle interventions. Although the metabolic effects of bariatric surgery have been observed for over 50 years, the primary molecular mechanisms underlying these effects are not well understood. A number of theories for the improvements in dysglycemia have been proposed, although accumulating evidence from both clinical observations and animal models supports a mechanistic role for alterations in bile acid levels. Bile acids have long been recognized as important mediators in the intestinal absorption of lipids but they also serve as ligands for the nuclear receptor farnesoid X receptor (FXR) and the cell surface receptor G protein–coupled bile acid receptor 1 (TGR5) which can have multiple and complex metabolic effects. The mechanisms by which post-bariatric changes in bile acids may affect glucose metabolism include regulating levels of fibroblast growth factor 19 (FGF19), glucagon-like peptide 1 (GLP-1), organ-specific effects, inflammation, and alterations in the gut microbiome. Due to their multiple and pleiotropic effects, the definitive role of bile acids in bariatric surgery is not yet known and will likely require randomized controlled clinical trials with specific bile acids and/or bile acid receptor modulators.