Frontiers in Physiology (Apr 2021)

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

  • Jordan D. Secor,
  • Scott C. Fligor,
  • Savas T. Tsikis,
  • Lumeng J. Yu,
  • Mark Puder

DOI
https://doi.org/10.3389/fphys.2021.656441
Journal volume & issue
Vol. 12

Abstract

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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.

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