title: Bile acids as metabolic regulators.
abstract: OBJECTIVE
  This review focuses on the latest understanding of the molecular mechanisms underlying the complex interactions between intestine and liver bile acid signaling, gut microbiota, and their impact on whole-body lipid, glucose and energy metabolism.
  
  
  RESULTS
  Hepatic bile acid synthesis is tightly regulated by the bile acid negative feedback mechanisms. Modulating the enterohepatic bile acid signaling greatly impacts the whole-body metabolic homeostasis. Recently, a positive feedback mechanism through intestine farnesoid X receptor (FXR) antagonism has been proposed to link gut microbiota to the regulation of bile acid composition and pool size. Two studies identified intestine Diet1 and hepatic SHP-2 as novel regulators of CYP7A1 and bile acid synthesis through the gut-liver FXR-fibroblast growth factor 15/19-FGF receptor four signaling axis. New evidence suggests that enhancing bile acid signaling in the distal ileum and colon contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery.
  
  
  CONCLUSIONS
  Small-molecule ligands that target TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut-liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type 2 diabetes.
authors.affiliation: aDepartment of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas bDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.
authors.forename: Tiangang
authors.initials: T
authors.lastname: Li
authors.forename: John Y L
authors.initials: JY
authors.lastname: Chiang
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated