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Free fatty acids induce cholecystokinin secretion through GPR120

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Abstract

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.

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Acknowledgements

This work was supported in part by research grants from the Scientific Fund of the Ministry of Education, Science, and Culture of Japan (to G.T., T.A., and T.-a.K.); the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) (to G.T., A.H., T.A. and T.-a.K.); and the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science”(to G.T., T.A. and T.T).

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Correspondence to Gozoh Tsujimoto.

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Tanaka, T., Katsuma, S., Adachi, T. et al. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn-Schmied Arch Pharmacol 377, 523–527 (2008). https://doi.org/10.1007/s00210-007-0200-8

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  • DOI: https://doi.org/10.1007/s00210-007-0200-8

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