Open AccessBile acid receptors and nonalcoholic fatty liver disease
Author(s) -
Liyun Yuan,
Kiran Bambha
Publication year - 2015
Publication title -
world journal of hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.913
H-Index - 55
ISSN - 1948-5182
DOI - 10.4254/wjh.v7.i28.2811
Subject(s) - farnesoid x receptor , nonalcoholic fatty liver disease , medicine , bile acid , g protein coupled bile acid receptor , fatty liver , insulin resistance , liver disease , chronic liver disease , pathogenesis , lipid metabolism , bioinformatics , endocrinology , nuclear receptor , disease , diabetes mellitus , biology , biochemistry , cirrhosis , transcription factor , gene
With the high prevalence of obesity, diabetes, and other features of the metabolic syndrome in United States, nonalcoholic fatty liver disease (NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis (NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor (TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH.