Bile acid signaling and bariatric surgery

Abstract

The rapid worldwide rise in obesity rates over the past few decades imposes an urgent need to develop effective strategies for treating obesity and associated metabolic complications. Bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), currently provide the most effective treatment for obesity and type 2 diabetes (T2D), as well as for non-alcoholic steatohepatitis (NASH). However, the underlying mechanisms of the beneficial effects of bariatric surgery remain elusive. Recent studies have identified bile acids as potential signaling molecules involved in the beneficial effects of bariatric surgery. This review focuses on the most recent studies on the roles of bile acids and bile acid receptors Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 5 (TGR5) in bariatric surgery. We also discuss the possibility of modulating bile acid signaling as a pharmacological therapeutic approach to treating obesity and its associated metabolic complications.

Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

“…[7][8][9] However, multiple authors have revealed that while these processes play a role in post-surgical T2D remission, they are not sufficient, in-and-of-themselves, to cause remission. [10] [11][12][13] Furthermore, there has been little directed effort to identifying which of these changes, if any, are responsible for the early, weight-loss independent T2D improvement seen clinically. Investigators have tried to address this by using sham pair-feeding and have shown that SG can lead to adipose adaptive immune cell changes, improved muscle and hepatic insulin sensitivity, and reduced hepatic steatosis in the absence of significant weight loss.…”

Gastrointestinal Mechanisms Underlying the Cardiovascular Effect of Metformin

“…It has been suggested that bile acids contribute to the metabolic benefits of bariatric surgery via systemic FXR activation [ 43 ]. However, relative to cirrhosis, the increase in serum bile acid concentrations reported following bariatric surgery is modest, e.g., mean fasting serum bile acid concentrations of 8.90 µmol/L, when compared to 110 µmol/L in patients with cryptogenic or alcoholic cirrhosis [ 44 , 45 , 46 ]. This may indicate that the concentration of systemic bile acids is critical, being cardiotoxic at pathologically high concentrations while conveying cardiovascular benefits at physiologically elevated concentrations.…”

The Role of the Small Bowel in Unintentional Weight Loss after Treatment of Upper Gastrointestinal Cancers

“…Bile acids are now considered major signaling molecules as they activate Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 5 (TGR5). This leads to stimulating secretion of GLP-1 and regulates glucose and energy homeostasis, lipid metabolism, and gut microbiota [36,37,38,39]. Visceral signaling of satiation is further enhanced by small bowel gut microbiota.…”