Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease

• Published in: Frontiers in physiology Vol. 12; p. 656441
• Main Authors: Secor, Jordan D, Fligor, Scott C, Tsikis, Savas T, Yu, Lumeng J, Puder, Mark
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.04.2021
• Subjects: fatty acid; free fatty acid receptor; G protein-coupled receptor; liver disease; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; Physiology; G protein-coupled receptor; non-alcoholic fatty liver disease; liver disease; intestinal failure-associated liver disease; fatty acid; free fatty acid receptor; non-alcoholic steatohepatitis
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2021.656441

Free fatty acid receptors (FFARs) are a class of G protein-coupled receptors (GPCRs) that have wide-ranging effects on human physiology. The four well-characterized FFARs are FFAR1/GPR40, FFAR2/GPR43, FFAR3/GPR41, and FFAR4/GPR120. Short-chain (<6 carbon) fatty acids target FFAR2/GPR43 and FFAR3/GPR41. Medium- and long-chain fatty acids (6-12 and 13-21 carbon, respectively) target both FFAR1/GPR40 and FFAR4/GPR120. Signaling through FFARs has been implicated in non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), intestinal failure-associated liver disease (IFALD), and a variety of other liver disorders. FFARs are now regarded as targets for therapeutic intervention for liver disease, diabetes, obesity, hyperlipidemia, and metabolic syndrome. In this review, we provide an in-depth, focused summary of the role FFARs play in liver health and disease.