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

Joseph Pierre, Kristina B. Martinez, Honggang Ye, Anuradha Nadimpalli, Timothy C. Morton, Jinghui Yang, Qiang Wang, Noelle Patno, Eugene B. Chang, Deng Ping Yin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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-α, 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.

Original languageEnglish (US)
Pages (from-to)G286-G304
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016

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Obese Mice
High Fat Diet
Bile Acids and Salts
Phenotype
White Adipose Tissue
Thermogenesis
Glucose
Energy Metabolism
Intestines
Homeostasis
Bacteroidetes
Lipids
Brown Adipose Tissue
Gastric Bypass
Morbid Obesity
Groin
Jejunum
Portal Vein
Body Composition
Gallbladder

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. / Pierre, Joseph; Martinez, Kristina B.; Ye, Honggang; Nadimpalli, Anuradha; Morton, Timothy C.; Yang, Jinghui; Wang, Qiang; Patno, Noelle; Chang, Eugene B.; Yin, Deng Ping.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 311, No. 2, 01.08.2016, p. G286-G304.

Research output: Contribution to journalArticle

Pierre, Joseph ; Martinez, Kristina B. ; Ye, Honggang ; Nadimpalli, Anuradha ; Morton, Timothy C. ; Yang, Jinghui ; Wang, Qiang ; Patno, Noelle ; Chang, Eugene B. ; Yin, Deng Ping. / Activation of bile acid signaling improves metabolic phenotypes in high-fat diet-induced obese mice. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2016 ; Vol. 311, No. 2. pp. G286-G304.
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