title: Free fatty acid receptors and their role in regulation of energy metabolism.
abstract: The free fatty acid receptor (FFAR) is a G protein-coupled receptor (GPCR) activated by free fatty acids (FFAs), which play important roles not only as essential nutritional components but also as signaling molecules in numerous physiological processes. In the last decade, FFARs have been identified by the GPCR deorphanization strategy derived from the human genome database. To date, several FFARs have been identified and characterized as critical components in various physiological processes. FFARs are categorized according to the chain length of FFA ligands that activate each FFAR; FFA2 and FFA3 are activated by short chain FFAs, GPR84 is activated by medium-chain FFAs, whereas FFA1 and GPR120 are activated by medium- or long-chain FFAs. FFARs appear to act as physiological sensors for food-derived FFAs and digestion products in the gastrointestinal tract. Moreover, they are considered to be involved in the regulation of energy metabolism mediated by the secretion of insulin and incretin hormones and by the regulation of the sympathetic nerve systems, taste preferences, and inflammatory responses related to insulin resistance. Therefore, because FFARs can be considered to play important roles in physiological processes and various pathophysiological processes, FFARs have been targeted in therapeutic strategies for the treatment of metabolic disorders including type 2 diabetes and metabolic syndrome. In this review, we present a summary of recent progress regarding the understanding of their physiological roles in the regulation of energy metabolism and their potential as therapeutic targets.
authors.affiliation: World-Leading Drug Discovery Research Center, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan, t-hara@pharm.kyoto-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hara
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Inoue
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Ichimura
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005230:Fatty Acids, Nonesterified; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C473103:FFAR2 protein, human; C473034:FFAR1 protein, human; C106262:FFAR3 protein, human; C519853:FFAR4 protein, human; C431700:GPR84 protein, human