Inhibition of gastric inhibitory polypeptide signaling prevents obesity

Kazumasa Miyawaki, Yuichiro Yamada, Nobuhiro Ban, Yu Ihara, Katsushi Tsukiyama, Heying Zhou, Shimpei Fujimoto, Akira Oku, Kinsuke Tsuda, Shinya Toyokuni, Hiroshi Hiai, Wataru Mizunoya, Tohru Fushiki, Jens Juul Holst, Mitsuhiro Makino, Akira Tashita, Yukari Kobara, Yoshiharu Tsubamoto, Takayoshi Jinnouchi, Takahito JomoriYutaka Seino

研究成果: ジャーナルへの寄稿学術誌査読

756 被引用数 (Scopus)


Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr−/−) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr−/−, Lepob/Lepob) generated by crossbreeding Gipr−/− and obese ob/ob (Lepob/Lepob) mice gained less weight and had lower adiposity than Lepob/Lepob mice. The Gipr−/− mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs.

ジャーナルNature medicine
出版ステータス出版済み - 7月 2002

!!!All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)


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