New frontiers in gut nutrient sensor research: free fatty acid sensing in the gastrointestinal tract.
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.
Miyauchi
Satoshi
S
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Hirasawa
Akira
A
Ichimura
Atsuhiko
A
Hara
Takafumi
T
Tsujimoto
Gozoh
G
D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000032:analysis / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000378:metabolism
C473034:FFAR1 protein, human; D005230:Fatty Acids, Nonesterified; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled