GPCRs get fatty: the role of G protein-coupled receptor signaling in the development and progression of nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD), characterized by the abnormal deposition of lipids within the liver not due to alcohol consumption, is a growing epidemic affecting over 30% of the United States population. Both simple fatty liver and its more severe counterpart, nonalcoholic steatohepatitis, represent one of the most common forms of liver disease. Recently, several G protein-coupled receptors have emerged as targets for therapeutic intervention for these disorders. These include those with known hepatic function as well as those involved in global metabolic regulation. In this review, we highlight these emerging therapeutic targets, focusing on several common themes including their activation by microbial metabolites, stimulatory effect on insulin and incretin secretion, and contribution to glucose tolerance. The overlap in ligands, localization, and downstream effects of activation indicate the interdependent nature of these receptors and highlight the importance of this signaling family in the development and prevention of NAFLD.