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- Title
Inhibition of gastric inhibitory polypeptide signaling prevents obesity.
- Authors
Miyawaki, Kazumasa; Yamada, Yuichiro; Ban, Nobuhiro; Ihara, Yu; Tsukiyama, Katsushi; Zhou, Heying; Fujimoto, Shimpei; Oku, Akira; Tsuda, Kinsuke; Toyokuni, Shinya; Hiai, Hiroshi; Mizunoya, Wataru; Fushiki, Tohru; Holst, Jens Juul; Makino, Mitsuhiro; Tashita, Akira; Kobara, Yukari; Tsubamoto, Yoshiharu; Jinnouchi, Takayoshi
- Abstract
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.
- Subjects
OBESITY; METABOLIC disorders; PEPTIDES; DRUG therapy
- Publication
Nature Medicine, 2002, Vol 8, Issue 7, p738
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm727