5 years ago

Glucose-dependent insulinotropic polypeptide is required for moderate high fat diet, but not high carbohydrate diet-induced weight gain.

Nobuya Inagaki, Erina Joo, Yusuke Seino, Yoshitaka Hayashi, Hiroshi Arima, Yutaka Oiso, Yoji Hamada, Akiko Sankoda, Hidetada Ogata, Takako Izumoto, Norio Harada, Masatoshi Murase, Ryuya Maekawa, Atsushi Iida, Kazuyo Suzuki, Shin Tsunekawa
Both high fat diet and high carbohydrate diet are known to induce weight gain. Glucose-dependent insulinotropic polypeptide (GIP) is secreted mainly from intestinal K-cells upon stimuli by nutrients such as fat and glucose, and it potentiates glucose-induced insulin secretion. GIP is well-known to contribute to high fat diet-induced obesity. In this study, we analyzed the effect of high carbohydrate feeding on GIP secretion and metabolic parameters to explore the role of GIP in high carbohydrate-induced weight gain. Both wild-type (WT) and GIP receptor deficient (GiprKO) mice were fed normal chow (NC), high-starch diet (ST) and moderate high-fat diet (mHFD) for 22 weeks. Body weight was measured and then glucose tolerance tests were performed. Insulin secretion from isolated islets also was analyzed. WT mice fed ST or mHFD displayed weight gain concomitant with increased plasma GIP levels compared to WT mice fed NC. WT mice fed mHFD showed improved glucose tolerance due to enhanced insulin secretion during oral glucose tolerance tests compared to WT mice fed NC or ST. GiprKO mice fed mHFD did not display weight gain. On the other hand, GiprKO mice fed ST showed weight gain and did not display obvious glucose intolerance. Glucose-induced insulin secretion was enhanced during intraperitoneal glucose tolerance tests and from isolated islets in both WT and GiprKO mice fed ST compared with those fed NC. In conclusion, enhanced GIP secretion induced by mHFD-feeding contributes to increased insulin secretion and body weight gain whereas GIP is marginally involved in weight gain induced by ST-feeding.

Publisher URL: http://doi.org/10.1152/ajpendo.00352.2017

DOI: 10.1152/ajpendo.00352.2017

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