title: Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion.
abstract: Gastric inhibitory polypeptide (GIP) is an incretin secreted from enteroendocrine K cells in response to meal ingestion. Recently free fatty acid receptor G protein-coupled receptor (GPR) 120 was identified as a lipid sensor involved in glucagon-like peptide-1 secretion. However, Gpr 120 gene expression and its role in K cells remain unclear, partly due to difficulties in separation of K cells from other intestinal epithelial cells. In this study, we purified K cells using GIP-green fluorescent protein (GFP) knock-in mice, in which K cells can be visualized by GFP fluorescence. GFP-positive cells (K cells) were observed in the small intestine but not in the stomach and colon. K cell number and GIP content in K cells were significantly higher in the upper small intestine than those in the lower small intestine. We also examined the expression levels of several free fatty acid receptors in K cells. Among free fatty acid receptors, GPR120 was highly expressed in the K cells of the upper small intestine compared with the lower small intestine. To clarify the role of GPR120 on K cells in vivo, we used GPR120-deficient mice (GPR120(-/-)). GPR120(-/-) exhibited significantly lower GIP secretion (75% reduction, P < .01) after lard oil ingestion compared with that in wild-type mice. Consistently, pharmacological inhibition of GPR120 with grifolic acid methyl ether in wild-type mice significantly attenuated lard oil-induced GIP secretion. In conclusion, GPR120 is expressed abundantly in K cells of the upper small intestine and plays a critical role in lipid-induced GIP secretion.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition (K.Iw., N.H., K.Sa., S.Y., K.Su., A.Ha., D.N., K.Sh., E.J., T.Har., N.I.), Graduate School of Medicine, and Department of Genomic Drug Discovery Science (K.Ii., A.Hi.), Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8507, Japan; and Faculty of Pharmaceutical Sciences (T.Has., Y.A.), Tokushima Bunri University, Tokushima 770-8514, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Harada
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamane
authors.forename: Keiko
authors.initials: K
authors.lastname: Iida
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hamasaki
authors.forename: Daniela
authors.initials: D
authors.lastname: Nasteska
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Shibue
authors.forename: Erina
authors.initials: E
authors.lastname: Joo
authors.forename: Takanari
authors.initials: T
authors.lastname: Harada
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D004041:Dietary Fats; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D005951:Glucose Tolerance Test; D049452:Green Fluorescent Proteins; D007413:Intestinal Mucosa; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012459:Salicylates / Q000494:pharmacology; D054830:Sesterterpenes / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; C498007:FFAR4 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012459:Salicylates; D054830:Sesterterpenes; C000597016:grifolic acid methyl ether; D049452:Green Fluorescent Proteins; D005749:Gastric Inhibitory Polypeptide; C029310:lard