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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.

journal_name

Nat Med

journal_title

Nature medicine

authors

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

doi

10.1038/nm727

keywords:

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

738-42

issue

7

eissn

1078-8956

issn

1546-170X

pii

nm727

journal_volume

8

pub_type

杂志文章

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