%0 Journal Article
%T Bile Acid Signaling in Liver Metabolism and Diseases
%A Tiangang Li
%A John Y. L. Chiang
%J Journal of Lipids
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/754067
%X Obesity, diabetes, and metabolic syndromes are increasingly recognized as health concerns worldwide. Overnutrition and insulin resistance are the major causes of diabetic hyperglycemia and hyperlipidemia in humans. Studies in the past decade provide evidence that bile acids are not just biological detergents facilitating gut nutrient absorption, but also important metabolic regulators of glucose and lipid homeostasis. Pharmacological alteration of bile acid metabolism or bile acid signaling pathways such as using bile acid receptor agonists or bile acid binding resins may be a promising therapeutic strategy for the treatment of obesity and diabetes. On the other hand, bile acid signaling is complex, and the molecular mechanisms mediating the bile acid effects are still not completely understood. This paper will summarize recent advances in our understanding of bile acid signaling in regulation of glucose and lipid metabolism, and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders. 1. Introduction Bile acids are produced only in the liver as the end products of cholesterol catabolism [1, 2]. In addition to the classic function of bile acids in facilitating hepatobiliary secretion of endogenous metabolites and xenobiotics and intestine absorption of lipophilic nutrients, bile acids also play equally important roles in controlling the metabolism of glucose and lipids in the enterohepatic system, and energy expenditure in peripheral tissues [3, 4]. Because of such a close association between bile acid signaling and metabolic homeostasis, targeting bile acid metabolism by using bile acid receptor agonists or bile acid-binding resins have proven to be effective in improving lipid and glucose homeostasis in obesity and diabetes [5]. Furthermore, stimulating de novo bile acid synthesis prevented, whereas, disruption of bile acid signaling caused insulin resistance and dyslipidemia in mice, indicating that impaired bile acid homeostasis may likely contribute to the pathogenesis of metabolic disorders [6¨C9]. This paper will summarize recent advances in our understanding of bile acid signaling regulation of glucose and lipid metabolism and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders. 2. Bile Acid Synthesis Bile acids are the end product of cholesterol catabolism in the liver [1, 10¨C12]. In humans, the bile acid pool consists of primary bile acids cholic acid (CA), chenodeoxycholic acid (CDCA),
%U http://www.hindawi.com/journals/jl/2012/754067/