Free Fatty Acid Receptors and Their Role in Regulation of Energy Metabolism

  • Takafumi HaraEmail author
  • Ikuo Kimura
  • Daisuke Inoue
  • Atsuhiko Ichimura
  • Akira Hirasawa
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 164)


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.


Insulin Secretion Quantitative Reverse Transcription Polymerase Chain Reaction GPR120 Expression Free Fatty Acid Receptor Ionic Lock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by JSPS KAKENHI Grant Number 24790249. The methods for animal care and experiments were approved by the Animal Care Committee of Kyoto University.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Takafumi Hara
    • 1
    • 2
    Email author
  • Ikuo Kimura
    • 3
  • Daisuke Inoue
    • 3
  • Atsuhiko Ichimura
    • 4
  • Akira Hirasawa
    • 3
  1. 1.World-Leading Drug Discovery Research Center, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  2. 2.Center for Genomic Medicine, Graduate School of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  4. 4.Department of Molecular Medicine and TherapyTohoku University Graduate School of MedicineSendaiJapan

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