Bile acids and bariatric surgery

Abstract

Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40-80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short-and long-term metabolic improvements after bariatric surgery is critically examined.

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

“…1,[36][37][38] Several mechanisms may account for the elevation of PYY in islets after bariatric surgery, including changes in bile acids and microbiota-derived metabolites. Quantitative and qualitative modification of these factors has been well documented post gastric bypass in rodents and humans [39][40][41][42] and, in some cases, they have been shown to directly regulate PYY expression in gut cells. 43,44 Whether PYY content in islets is also affected by these factors remains an interesting avenue to explore.…”

Proceedings of the 2017 ASPEN Research Workshop—Gastric Bypass: Role of the Gut

“…85 The benefits of bariatric surgery extend beyond weight loss and are postulated to occur via modulation of glucose and lipid homeostasis, which in turn are also regulated by bile acids. 86 Given alterations noted in serum bile acid levels after gastric bypass surgery in both human and animal studies, 12,87 several authors have postulated that the beneficial effects after surgery are a result, at least in part, of changes in enterohepatic circulation of bile acids. 88 Experimental approaches such as "ileal transposition" or bile diversion have been used in preclinical studies.…”

Bile acid signaling and bariatric surgery

“…Among the many potential mediators, bile acid signaling seems to play an important role in modulating the beneficial effects of bariatric surgery. 4,12–15 The success of surgery in alleviating obesity and T2D prompts us to reconsider the neglected role of the gut in nutritional sensing and metabolic regulation. Furthermore, bariatric surgery provides us with an ideal model to delineate the novel etiological mechanisms of obesity and related metabolic diseases as well as a paradigm to develop novel treatment approaches.…”