Free fatty acids induce cholecystokinin secretion through GPR120.
The ingestion of fat induces secretion of the gut peptide hormone cholecystokinin (CCK); however, the mechanism responsible for lipid-induced CCK release remains unknown. Recently, a group of free fatty acid (FFA) receptors, which includes the long-chain FFA receptors GPR120 and GPR40, has been identified. In this study, we examined whether these FFA receptors mediate lipid-induced CCK release in the mouse. We first observed that intra-gastric administration of long-chain FFAs increased plasma CCK levels. Using mouse enteroendocrine STC-1 cells as a model system, we further studied the mechanism of this FFA-induced CCK secretion. Long-chain FFAs promoted CCK secretion from STC-1 cells, which was abolished either by removal of extracellular Ca2+ or by the L-type Ca2+ channel blocker nicardipine. Furthermore, this FFA-induced CCK secretion was specifically inhibited by transfection of GPR120-specific, but not GPR40-specific, short hairpin RNA. These results indicate that long-chain FFAs induce CCK secretion through GPR120-coupled Ca2+ signaling.
Tanaka
Toshiki
T
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Katsuma
Susumu
S
Adachi
Tetsuya
T
Koshimizu
Taka-aki
TA
Hirasawa
Akira
A
Tsujimoto
Gozoh
G
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002766:Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection
C498007:FFAR4 protein, mouse; D005230:Fatty Acids, Nonesterified; C473036:Ffar1 protein, mouse; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D002766:Cholecystokinin