TY - JOUR
T1 - Inhibition of gastric inhibitory polypeptide signaling prevents obesity
AU - Miyawaki, Kazumasa
AU - Yamada, Yuichiro
AU - Ban, Nobuhiro
AU - Ihara, Yu
AU - Tsukiyama, Katsushi
AU - Zhou, Heying
AU - Fujimoto, Shimpei
AU - Oku, Akira
AU - Tsuda, Kinsuke
AU - Toyokuni, Shinya
AU - Hiai, Hiroshi
AU - Mizunoya, Wataru
AU - Fushiki, Tohru
AU - Holst, Jens Juul
AU - Makino, Mitsuhiro
AU - Tashita, Akira
AU - Kobara, Yukari
AU - Tsubamoto, Yoshiharu
AU - Jinnouchi, Takayoshi
AU - Jomori, Takahito
AU - Seino, Yutaka
N1 - Funding Information:
Acknowledgments We thank S. Seino for critically reading the manuscript and for helpful discussions; H. Yano, H. Niwa and J. Miyazaki for help in generating the knockout mice; and H. Kohda for technical assistance in morphological examinations. This study was supported in part by Grants-in-Aid for Creative Scientific Research (10NP0201) and for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a grant from ‘Research for the Future’ Program of the Japan Society for the Promotion of Science (JSPS-RFTF97I00201) and by Health Sciences Research Grants for Research on Human Genome, Tissue Engineering and Food Biotechnology from the Ministry of Health, Labor and Welfare.
PY - 2002/7
Y1 - 2002/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036068322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036068322&partnerID=8YFLogxK
U2 - 10.1038/nm727
DO - 10.1038/nm727
M3 - Article
C2 - 12068290
AN - SCOPUS:0036068322
SN - 1078-8956
VL - 8
SP - 738
EP - 742
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -
