Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

Yuki Murata; Norio Harada; Shigenobu Kishino; Kanako Iwasaki; Eri Ikeguchi-Ogura; Shunsuke Yamane; Tomoko Kato; Yoshinori Kanemaru; Akiko Sankoda; Tomonobu Hatoko; Sakura Kiyobayashi; Jun Ogawa; Akira Hirasawa; Nobuya Inagaki

doi:10.1016/j.isci.2021.102963

Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK

iScience. 2021 Aug 9;24(9):102963. doi: 10.1016/j.isci.2021.102963. eCollection 2021 Sep 24.

Affiliations

¹ Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
² Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
³ Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

Abstract

Long-chain triglycerides (LCTs) intake strongly stimulates GIP secretion from enteroendocrine K cells and induces obesity and insulin resistance partly due to GIP hypersecretion. In this study, we found that medium-chain triglycerides (MCTs) inhibit GIP secretion after single LCT ingestion and clarified the mechanism underlying MCT-induced inhibition of GIP secretion. MCTs reduced the CCK effect after single LCT ingestion in wild-type (WT) mice, and a CCK agonist completely reversed MCT-induced inhibition of GIP secretion. In vitro studies showed that medium-chain fatty acids (MCFAs) inhibit long-chain fatty acid (LCFA)-stimulated CCK secretion and increase in intracellular Ca²⁺ concentrations through inhibition of GPR120 signaling. Long-term administration of MCTs reduced obesity and insulin resistance in high-LCT diet-fed WT mice, but not in high-LCT diet-fed GIP-knockout mice. Thus, MCT-induced inhibition of GIP hypersecretion reduces obesity and insulin resistance under high-LCT diet feeding condition.

Keywords: Biological sciences; Endocrinology; Physiology.