TY - JOUR
T1 - Angiopoietin-related growth factor antagonizes obesity and insulin resistance
AU - Oike, Yuichi
AU - Akao, Masaki
AU - Yasunaga, Kunio
AU - Yamauchi, Toshimasa
AU - Morisada, Tohru
AU - Ito, Yasuhiro
AU - Urano, Takashi
AU - Kimura, Yoshishige
AU - Kubota, Yoshiaki
AU - Maekawa, Hiromitsu
AU - Miyamoto, Takeshi
AU - Miyata, Keishi
AU - Matsumoto, Shun Ichiro
AU - Sakai, Jura
AU - Nakagata, Naomi
AU - Takeya, Motohiro
AU - Koseki, Haruhiko
AU - Ogawa, Yoshihiro
AU - Kadowaki, Takashi
AU - Suda, Toshio
N1 - Funding Information:
We thank K. Fukushima for her assistance with the experiments. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan, by the Yamanouchi Foundation for Research on Metabolic Disorders and by the Mochida Memorial Foundation for Medical and Pharmaceutical Research.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
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U2 - 10.1038/nm1214
DO - 10.1038/nm1214
M3 - Article
C2 - 15778720
AN - SCOPUS:20244380182
SN - 1078-8956
VL - 11
SP - 400
EP - 408
JO - Nature Medicine
JF - Nature Medicine
IS - 4
ER -
