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

被引：166

作者：

Albaugh, Vance L. ^{[1
]}

Banan, Babak ^{[1
]}

Antoun, Joseph ^{[1
]}

Xiong, Yanhua ^{[1
]}

Guo, Yan ^{[2
]}

Ping, Jie ^{[2
]}

Alikhan, Muhammed ^{[1
]}

Clements, Blake Austin ^{[1
]}

Abumrad, Naji N. ^{[1
]}

Flynn, Charles Robb ^{[1
]}

机构：

[1] Vanderbilt Univ, Dept Surg, MRB4 Room 8465A,1161 21st Ave S,CCC 2308 MCN, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA

来源：

GASTROENTEROLOGY | 2019年 / 156卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Metabolic Surgery; Gut Microbiome; Lymph Fistula; Glucagon-Like Polypeptide 1 (Glp-1); Y-GASTRIC-BYPASS; GLUCAGON-LIKE PEPTIDE-1; GUT MICROBIOTA; WEIGHT-LOSS; AKKERMANSIA-MUCINIPHILA; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; DIABETES-MELLITUS; OBESITY; SLEEVE;

D O I：

10.1053/j.gastro.2018.11.017

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND & AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Rouxen- 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 (FxrD/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 FxrD/E mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weightindependent 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.

引用

页码：1041 / +

页数：15

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