open access

https://hdl.handle.net/2115/85388

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells : Specific Structures in Oxo-Fatty Acids Produced by Gut Bacteria Are Responsible for CCK Secretion in STC-1 Cells via GPR40

英語

2018-10

Molecular Nutrition & Food Research

62(19)

1800146

Scope The secretion of gut hormones, such as cholecystokinin (CCK) is stimulated by fatty acids. Although a chain length?dependent mechanism has been proposed, other structural relationships to releasing activity remain unclear. We aimed to elucidate specific structures in fatty acids that are responsible for their CCK-releasing activity, and related sensing mechanisms in enteroendocrine cells. Methods and results CCK secretory activities were examined in a murine CCK-producing cell line STC-1 by exposing the cells to various modified fatty acids produced by gut lactic acid bacteria. The effects of fatty acids on gastric emptying rate as a CCK-mediated function were examined using acetaminophen and phenol red methods in rats. Out of more than 30 octadecanoic-derived fatty acids tested, 5 oxo-fatty acids potently stimulated CCK secretion without cytotoxic effects in STC-1 cells. Three fatty acids had a distinct specific structure containing one double bond, whereas the other two had two double bonds, nearby an oxo residue. CCK secretion induced by representative fatty acids (10-oxo-trans-11-18:1 and 13-oxo-cis-9,cis-15-18:2) was attenuated by a fatty acid receptor G-protein coupled receptor 40 antagonist. Oral administration of 13-oxo-cis-9,cis-15-18:2 lowered the gastric emptying rate in rats in a dose- and structure-dependent manner. Conclusion These results reveal a novel fatty acid-sensing mechanism in enteroendocrine cells.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Hira, T., Ogasawara, S., Yahagi, A., Kamachi, M., Li, J., Nishimura, S., Sakaino, M., Yamashita, T., Kishino, S., Ogawa, J., Hara, H., Mol. Nutr. Food Res. 2018, 62, 1800146, which has been published in final form at https://doi.org/10.1002/mnfr.201800146. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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