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Angiopoietin-related growth factor antagonizes obesity and insulin resistance.

Abstract：

:Angiopoietin-related growth factor (AGF), a member of the angiopoietin-like protein (Angptl) family, is secreted predominantly from the liver into the systemic circulation. Here, we show that most (>80%) of the AGF-deficient mice die at about embryonic day 13, whereas the surviving AGF-deficient mice develop marked obesity, lipid accumulation in skeletal muscle and liver, and insulin resistance accompanied by reduced energy expenditure relative to controls. In parallel, mice with targeted activation of AGF show leanness and increased insulin sensitivity resulting from increased energy expenditure. They are also protected from high-fat diet-induced obesity, insulin resistance and nonadipose tissue steatosis. Hepatic overexpression of AGF by adenoviral transduction, which leads to an approximately 2.5-fold increase in serum AGF concentrations, results in a significant (P < 0.01) body weight loss and increases insulin sensitivity in mice fed a high-fat diet. This study establishes AGF as a new hepatocyte-derived circulating factor that counteracts obesity and related insulin resistance.

journal_name

Nat Med

journal_title

Nature medicine

authors

Oike Y,Akao M,Yasunaga K,Yamauchi T,Morisada T,Ito Y,Urano T,Kimura Y,Kubota Y,Maekawa H,Miyamoto T,Miyata K,Matsumoto S,Sakai J,Nakagata N,Takeya M,Koseki H,Ogawa Y,Kadowaki T,Suda T

doi

10.1038/nm1214

keywords:

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

400-8

issue

4

eissn

1078-8956

issn

1546-170X

pii

nm1214

journal_volume

11

pub_type

杂志文章

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