PT  - JOURNAL ARTICLE
AU  - Tiangang Li
AU  - John Y. L. Chiang
ED  - Ma, Qiang
TI  - Bile Acid Signaling in Metabolic Disease and Drug Therapy
AID  - 10.1124/pr.113.008201
DP  - 2014 Oct 01
TA  - Pharmacological Reviews
PG  - 948--983
VI  - 66
IP  - 4
4099  - http://pharmrev.aspetjournals.org/content/66/4/948.short
4100  - http://pharmrev.aspetjournals.org/content/66/4/948.full
SO  - Pharmacol Rev2014 Oct 01; 66
AB  - Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.