title: Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation.
abstract: Bile acids play a critical role in the regulation of glucose, lipid and energy metabolisms by activating the nuclear bile acid receptor farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (aka takeda G protein couple receptor 5, TGR5) signaling. Paradoxical roles of FXR in the regulation of glucose and lipid metabolism and metabolic disorder have been reported recently. The activation or inhibition of intestinal FXR signaling has been shown to improve insulin and glucose sensitivity and energy metabolism to prevent diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). TGR5 has an anti-inflammatory function in the intestine and stimulates glucagon-like peptide-1 (GLP-1) secretion in the intestine to stimulate insulin secretion from the pancreas. The role of TGR5 in metabolism and metabolic regulation is not clear and warrants further study. FXR and TGR5 are co-expressed in the ileum and colon. These 2 bile acid-activated receptors may cooperate to stimulate GLP-1 secretion and improve hepatic metabolism. FXR and TGR5 dual agonists may have therapeutic potential for treating diabetes and NAFLD.
authors.affiliation: Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.
authors.forename: John Y L
authors.initials: JY
authors.lastname: Chiang
authors.forename: Preeti
authors.initials: P
authors.lastname: Pathak
authors.forename: Hailiang
authors.initials: H
authors.lastname: Liu
authors.forename: Ajay
authors.initials: A
authors.lastname: Donepudi
authors.forename: Jessica
authors.initials: J
authors.lastname: Ferrell
authors.forename: Shannon
authors.initials: S
authors.lastname: Boehme
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D000099150:Receptor, Farnesoid X-Activated