Mechanisms of Action of Surgical Interventions on Weight-Related Diseases: the Potential Role of Bile Acids

Abstract

Surgical interventions for weight-related diseases (SWRD) may have substantial and sustainable effect on weight reduction, also leading to a higher remission rate of type 2 diabetes (T2D) mellitus than any other medical treatment or lifestyle intervention. The resolution of T2D after Roux-en-Y gastric bypass (RYGB) typically occurs too quickly to be accounted for by weight loss alone, suggesting that these operations have a direct impact on glucose homeostasis. The mechanisms underlying these beneficial effects however remain unclear. Recent research suggests that changes in the concentrations of plasma bile acids might contribute to these metabolic changes after surgery. In this review, we aimed to outline the potential role of bile acids in SWRD. We systematically reviewed MEDLINE, SCOPUS, and Web of Science for articles reporting the effect of SWRD on outcomes published between 1969 and 2016. We found that changes in circulating bile acids after surgery may play a major role through activation of the farnesoid X receptor A (FXRA), the fibroblast growth factor 19 (FGF19), and the G protein-coupled bile acid receptor (TGR5). Bile acid concentration increased significantly after RYGB. Some studies suggest that a transitory decrease occurs at 1 week post-surgery, followed by a gradual increase. Most studies have shown the increase to be proportionate by all bile acid subtypes. Bile acids can regulate glucose metabolism through the expression of TGR5 receptor in L cells, resulting in a release of glucagon-like peptide 1 (GLP-1). It may also induce the synthesis and secretion of FGF19 in ileal cells, thereby improving insulin sensitivity and regulating glucose metabolism. All the present SWRD are involved with changes in food stimulation to the stomach. This implies that discovering and developing the antagonists to TGR5 and FXRA may effectively control metabolic syndrome and the elucidation of the mechanisms underlying the physiological effects related to weight loss and T2D remission after surgery may help to identify new drug targets.

Effect of bariatric surgery on adiposity and metabolic profiles: A prospective cohort study in Middle-Eastern patients

“…Very recently, Mazidi et al[43] have reviewed role of bile acids its subtractions on weight loss and glycaemic control after the bariatric surgeries. They have elaborated that there is a correlation between the concentration of the total bile acid and improvements in several key metabolic parameters after bariatric surgery[43].…”

“…Very recently, Mazidi et al[43] have reviewed role of bile acids its subtractions on weight loss and glycaemic control after the bariatric surgeries. They have elaborated that there is a correlation between the concentration of the total bile acid and improvements in several key metabolic parameters after bariatric surgery[43]. It has been reported that there was an inverse correlation between bile acid concentrations and postprandial glucose and triglycerides, and a positive correlation with adiponectin and peak GLP-1 levels following a mixed meal test[33,44].…”

“…Moreover, augmented bile acid concentration (It has been suggested that changed upper intestinal tract structure after surgery might have an impact on the enterohepatic circulation of bile acids) could contribute to enhancements in insulin sensitivity, incretin secretion, lipid metabolism and postprandial glycemia after surgery[33,45]. As mentioned above, the release of GLP-1 is correlated with bile acids[43] (Figure 1). Therefore bile acid-dependent increases in postprandial GLP-1 concentrations may be somewhat responsible for the achievements of bariatric surgery in terms of both weight loss and glycaemic control[46].…”

Ultra-Early and Early Changes in Bile Acids and Insulin after Sleeve Gastrectomy among Obese Patients

“…Emerging data have shown that BAs work as key regulator molecules of glucose and lipid metabolism that act via binding to membrane or nuclear receptors [9][10][11][12]. In severely obese individuals, strong evidence has revealed that the same organs that display impaired insulin signaling are also targeted by BA, leading to significant disruptions in BA physiology [3].…”

“…Overall, bariatric surgery by both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most performed techniques at the moment, has been reported to induce important changes in BA metabolism related or nonrelated to weight loss [24,25]. These changes seem to promote metabolic health via improving insulin signaling and reducing IR, thus making, once more, BA an important therapeutic target [3,12,25]. However, while circulating BAs have been demonstrated to increase following RYGB [13,18,[26][27][28], the effect of SG on BA has shown mixed results.…”