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 Jomori; Yutaka Seino

doi:10.1038/nm727

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

670 Citations (Scopus)

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(-/-), 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.

Original language	English
Journal	Nature Medicine
Volume	8
Issue number	7
Pages (from-to)	738-42
Number of pages	4
ISSN	1078-8956
DOIs	https://doi.org/10.1038/nm727
Publication status	Published - 2002

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Miyawaki, K., Yamada, Y., Ban, N., Ihara, Y., Tsukiyama, K., Zhou, H., Fujimoto, S., Oku, A., Tsuda, K., Toyokuni, S., Hiai, H., Mizunoya, W., Fushiki, T., Holst, J. J., Makino, M., Tashita, A., Kobara, Y., Tsubamoto, Y., Jinnouchi, T., ... Seino, Y. (2002). Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature Medicine, 8(7), 738-42. https://doi.org/10.1038/nm727

Miyawaki, K, Yamada, Y, Ban, N, Ihara, Y, Tsukiyama, K, Zhou, H, Fujimoto, S, Oku, A, Tsuda, K, Toyokuni, S, Hiai, H, Mizunoya, W, Fushiki, T, Holst, JJ, Makino, M, Tashita, A, Kobara, Y, Tsubamoto, Y, Jinnouchi, T, Jomori, T & Seino, Y 2002, 'Inhibition of gastric inhibitory polypeptide signaling prevents obesity.', Nature Medicine, vol. 8, no. 7, pp. 738-42. https://doi.org/10.1038/nm727

@article{836d9dd0ab5211ddb5e9000ea68e967b,

title = "Inhibition of gastric inhibitory polypeptide signaling prevents obesity.",

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(-/-), 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.",

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

note = "Keywords: Adipose Tissue; Animals; Body Weight; Crosses, Genetic; Dietary Fats; Gastric Inhibitory Polypeptide; Mice; Mice, Knockout; Obesity; Receptors, Gastrointestinal Hormone; Signal Transduction",

year = "2002",

doi = "10.1038/nm727",

language = "English",

volume = "8",

pages = "738--42",

journal = "Nature Medicine",

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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

SN - 1078-8956

VL - 8

SP - 738

EP - 742

JO - Nature Medicine

JF - Nature Medicine

IS - 7

ER -

Inhibition of gastric inhibitory polypeptide signaling prevents obesity.

Abstract

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