title: Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders.
abstract: Over the last decade, a subfamily of G protein-coupled receptors that are agonized by endogenous and dietary free-fatty acids (FFA) has been discovered. These free-fatty acid receptors include FFA2 and FFA3, which are agonized by short-chained FFA, as well as FFA1 and FFA4, which are agonized by medium-to-long chained FFA. Ligands for FFA1 and FFA4 comprise the family of long chain polyunsaturated omega-3 fatty acids including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting that many of the long-known beneficial effects of these fats may be receptor mediated. In this regard, FFA4 has gathered considerable interest due to its role in ameliorating inflammation, promoting insulin sensitization, and regulating energy metabolism in response to FFA ligands. The goal of this review is to summarize the body of evidence in regard to FFA4 signal transduction, its mechanisms of regulation, and its functional role in a variety of tissues. In addition, recent endeavors toward discovery of small molecules that modulate FFA4 activity are also presented.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University Health Sciences Center, Mercer University, Atlanta, GA 30341, United States. Electronic address: Moniri_nh@mercer.edu.
authors.forename: Nader H
authors.initials: NH
authors.lastname: Moniri
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008744:Methylamines / Q000627:therapeutic use; D009928:Organ Specificity; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D011422:Propionates / Q000627:therapeutic use; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C519853:FFAR4 protein, human; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; C515630:GW9508; D008024:Ligands; D008744:Methylamines; D011422:Propionates; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled
keywords: Free fatty acids; Free-fatty acid receptor-4; G protein-coupled receptors; GPR120; Polyunsaturated fats
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