Angiopoietin-related growth factor antagonizes obesity and insulin resistance

Yuichi Oike, Masaki Akao, Kunio Yasunaga, Toshimasa Yamauchi, Toru Morisada, Yasuhiro Ito, Takashi Urano, Yoshishige Kimura, Yoshiaki Kubota, Hiromitsu Maekawa, Takeshi Miyamoto, Keishi Miyata, Shun Ichiro Matsumoto, Jura Sakai, Naomi Nakagata, Motohiro Takeya, Haruhiko Koseki, Yoshihiro Ogawa, Takashi Kadowaki, Toshio Suda

研究成果: Article

146 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)400-408
ページ数9
ジャーナルNature Medicine
11
発行部数4
DOI
出版物ステータスPublished - 2005 4

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

これを引用

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. I., Sakai, J., Nakagata, N., Takeya, M., Koseki, H., Ogawa, Y., Kadowaki, T., & Suda, T. (2005). Angiopoietin-related growth factor antagonizes obesity and insulin resistance. Nature Medicine, 11(4), 400-408. https://doi.org/10.1038/nm1214