期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 311, 期 2, 页码 G286-G304出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00202.2016
关键词
bile acids; bile diversion; obesity; energy expenditure; gut microbiota; gastric bypass; mice
资金
- Clinical and Translational Science Award [TR000430]
- National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK-42086, DK-097268, T32 DK-07074]
- Animal Models and Physiology Core at the University of Chicago [DK-020595]
- [F32 DK-105728-01A1]
The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1 alpha, PGC-1 beta, and PDGFR alpha in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype.
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