Inhibition of gastric inhibitory polypeptide signaling prevents obesity.
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Inhibition of gastric inhibitory polypeptide signaling prevents obesity. / 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; Jomori, Takahito; Seino, Yutaka.
In: Nature Medicine, Vol. 8, No. 7, 2002, p. 738-42.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Keywords: Adipose Tissue; Animals; Body Weight; Crosses, Genetic; Dietary Fats; Gastric Inhibitory Polypeptide; Mice; Mice, Knockout; Obesity; Receptors, Gastrointestinal Hormone; Signal Transduction
PY - 2002
Y1 - 2002
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(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) 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(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) 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.
U2 - 10.1038/nm727
DO - 10.1038/nm727
M3 - Journal article
C2 - 12068290
VL - 8
SP - 738
EP - 742
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 7
ER -
ID: 8418321