Dataset Information

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

ABSTRACT: BACKGROUND & AIMS:Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation. METHODS:Global G protein-coupled bile acid receptor-1 null (Tgr5-/-) and intestinal-specific farnesoid X receptor null (Fxr?/E) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/-) mice on chow diet were characterized following GB-IL. RESULTS:GB-IL induced weight loss and improved oral glucose tolerance in Tgr5-/-, but not Fxr?/E mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r-/- mice. CONCLUSIONS:Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

SUBMITTER: Albaugh VL

PROVIDER: S-EPMC6409186 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

Albaugh Vance L VL Banan Babak B Antoun Joseph J Xiong Yanhua Y Guo Yan Y Ping Jie J Alikhan Muhammed M Clements Blake Austin BA Abumrad Naji N NN Flynn Charles Robb CR

Gastroenterology 20181113 4

<h4>Background & aims</h4>Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation.<h4>Methods</h4>Global G protein-coupled bile acid receptor-1 null (Tgr5<sup>-/-</sup>) and intestinal-specific farnesoid X rece ...[more]

PMID: 30445014

Similar Datasets

Project description:ContextAltered cytokine levels and chronic low-grade inflammation contribute to metabolic dysfunction in obesity. The extent of cytokine changes and their impact on metabolic improvements after bariatric surgery have not been fully explored.ObjectiveTo compare 76 circulating cytokines, chemokines, and secreted cytokine receptors in subjects with obesity and lean subjects and determine how these cytokines are altered by bariatric surgery.Design, setting, and participantsA total of 37 patients with obesity and 37 lean patients in a cross-sectional study at an academic medical center. We also investigated cytokine changes in 25 patients with obesity after bariatric surgery.InterventionBariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy).Main outcome measuresQuantification of 76 circulating cytokines, chemokines, and secreted cytokine receptors.ResultsA total of 13 cytokines were significantly higher, and 4 lower, in patients with obesity relative to lean controls. Soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble TNF receptor (sTNFR) 1, and sTNFR2 were positively correlated, and soluble receptor for advanced glycation end-products was inversely correlated, with weight and body mass index. sTNFR2 was positively correlated with fasting glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c. After bariatric surgery, adiponectin increased, and leptin decreased. Elevated sVEGFR2 levels in patients with obesity were decreased (P = 0.01), whereas reduced chemokine (C-X-C motif) ligand (CXCL) 12 levels in patients with obesity increased (P = 0.03) after surgery. Patients with higher soluble interleukin receptor (sIL) 1R2 and sIL-6R levels before surgery had greater weight loss after surgery (P < 0.05).ConclusionsWe demonstrate that chemokine (C-C motif) ligand (CCL) 14, sVEGFR2, and platelet-derived growth factor BB are elevated in obesity, and CXCL12, CCL11, and CCL27 are lower in obesity. We found clinically concordant directionality between lean and patients with obesity and before vs after surgery for six cytokines, suggesting that bariatric surgery shifted the cytokine profiles of patients with obesity toward that of lean controls.

Dataset Information

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

Publications

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets