Changes in Bile Acid Metabolism, Transport, and Signaling as Central Drivers for Metabolic Improvements After Bariatric Surgery

Abstract

Purpose of Review: We review current evidence regarding changes in bile acid (BA) metabolism, transport, and signaling after bariatric surgery and how these might bolster fat mass loss and energy expenditure to promote improvements in type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Recent Findings: The two most common bariatric techniques, Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), increase the size and alter the composition of the circulating BA pool that may then impact energy metabolism through altered activities of BA targets in the many tissues perfused by systemic blood. Recent reports in human patients indicate that gene expression of the major BA target, the farnesoid X receptor (FXR), is increased in the liver but decreased in the small intestine after RYGB. In contrast, intestinal expression of the transmembrane G protein-coupled BA receptor (TGR5) is upregulated after surgery. Despite these apparent conflicting changes in receptor transcription, changes in BAs after both RYGB and VSG are associated with elevated postprandial systemic levels of fibroblast growth factor 19 (from FXR activation) and glucagon-like peptide 1 (from TGR5 activation). These signaling activities are presumed to support fat mass loss and related metabolic benefits of bariatric surgery, and this supposition is in agreement with findings from rodent models of RYGB and VSG. However, inter-species differences in BA physiology limit direct translation and mechanistic understanding of how changes in individual BA species contribute to post-operative improvements of T2D and NAFLD in humans. Thus, details of all these changes and their influences on BAs’ biological actions are still under scrutiny. Summary: Changes in BA physiology and receptor activities after RYGB and VSG likely support weight loss and promote sustained metabolic improvements.