Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice.

Autor:	Pierre JF; Department of Medicine, University of Chicago, Chicago, Illinois;, Martinez KB; Department of Medicine, University of Chicago, Chicago, Illinois;, Ye H; Department of Medicine, University of Chicago, Chicago, Illinois;, Nadimpalli A; Department of Medicine, University of Chicago, Chicago, Illinois;, Morton TC; Department of Ecology and Evolution, University of Chicago, Chicago, Illinois., Yang J; Department of Surgery, University of Chicago, Chicago, Illinois; and., Wang Q; Department of Surgery, University of Chicago, Chicago, Illinois; and., Patno N; Department of Medicine, University of Chicago, Chicago, Illinois;, Chang EB; Department of Medicine, University of Chicago, Chicago, Illinois;, Yin DP; Department of Surgery, University of Chicago, Chicago, Illinois; and dyin@surgery.bsd.uchicago.edu.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2016 Aug 01; Vol. 311 (2), pp. G286-304. Date of Electronic Publication: 2016 Jun 23.
DOI:	10.1152/ajpgi.00202.2016
Abstrakt:	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-1α, PGC-1β, and PDGFRα 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. (Copyright © 2016 the American Physiological Society.)
Databáze:	MEDLINE
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