New Frontiers in Gut Nutrient Sensor Research: Free Fatty Acid Sensing in the Gastrointestinal Tract

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  • Miyauchi Satoshi
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Hirasawa Akira
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Ichimura Atsuhiko
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Hara Takafumi
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Tsujimoto Gozoh
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

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  • Free fatty acid sensing in the gastrointestinal tract

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Abstract

Utilizing the human genome database, the recently developed G-protein–coupled receptors (GPCRs) deorphanizing strategy successfully identified multiple receptors of free fatty acids (FFAs). FFAs have been demonstrated to act as ligands of several GPCRs (FFAR1, FFAR2, FFAR3, and GPR120). These fatty acid receptors are proposed to play critical roles in various types of physiological homeostases. FFAR1 and GPR120 are activated by medium- and long-chain FFAs. In contrast, FFAR2 and FFAR3 are activated by short-chain FFAs. It has been elucidated that these four receptors are expressed in the gastrointestinal tract and have many essential roles as sensors of FFA. In this review, we summarize the physiological and pharmacological function of the receptors in the gastrointestinal tract.

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