Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2020-03, Vol.318 (3), p.G554-G573
• Main Authors: Chiang, John Y L, Ferrell, Jessica M
• Format: Article
• Language: English
• Subjects: Acids; Animals; Bile; Bile acids; Bile Acids and Salts - metabolism; Cardiovascular diseases; Cholesterol; Circadian rhythms; Detergents; Diabetes; Diabetes mellitus; Dysbacteriosis; Dyslipidemia; Energy metabolism; Fatty liver; Fatty Liver - diagnosis; Fatty Liver - drug therapy; Fatty Liver - metabolism; Gastrointestinal Agents - therapeutic use; Glucose metabolism; High fat diet; Homeostasis; Humans; Hyperglycemia; Lipid metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Membrane proteins; Metabolic disorders; Nutrients; Obesity; Receptors, Cytoplasmic and Nuclear - agonists; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Review; Signal Transduction; Sleep; Xenobiotics
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00223.2019

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G protein-coupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver.