Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease

Gastroenterology. 2017 May;152(7):1679-1694.e3. doi: 10.1053/j.gastro.2017.01.055. Epub 2017 Feb 15.

Abstract

Bile acids are signaling molecules that coordinately regulate metabolism and inflammation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in bile acid, lipid and carbohydrate metabolism, energy expenditure, and inflammation by acting predominantly in enterohepatic tissues, but also in peripheral organs. In this review, we discuss the most recent findings on the inter-organ signaling and interplay with the gut microbiota of bile acids and their receptors in meta-inflammation, with a focus on their pathophysiologic roles in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic steatohepatitis, and their potential therapeutic applications.

Keywords: Bile Acids; FXR; Meta-Inflammation; TGR5.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dyslipidemias / metabolism*
  • Energy Metabolism
  • Gastrointestinal Microbiome
  • Glucose / metabolism
  • Humans
  • Inflammation / metabolism*
  • Lipid Metabolism
  • Molecular Targeted Therapy
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction

Substances

  • Bile Acids and Salts
  • GPBAR1 protein, human
  • Gpbar1 protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor
  • Glucose