Angiopoietin-related growth factor antagonizes obesity and insulin resistance

Yuichi Oike, Masaki Akao, Kunio Yasunaga, Toshimasa Yamauchi, Tohru 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

Research output: Contribution to journalArticle

145 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)400-408
Number of pages9
JournalNature medicine
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2005
Externally publishedYes

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Angiopoietins
Insulin Resistance
Intercellular Signaling Peptides and Proteins
Obesity
Insulin
High Fat Diet
Energy Metabolism
Liver
Nutrition
Thinness
Fats
Weight Loss
Hepatocytes
Skeletal Muscle
Body Weight
Lipids
Muscle
Chemical activation
Tissue
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Oike, Y., Akao, M., Yasunaga, K., Yamauchi, T., Morisada, T., Ito, Y., ... Suda, T. (2005). Angiopoietin-related growth factor antagonizes obesity and insulin resistance. Nature medicine, 11(4), 400-408. https://doi.org/10.1038/nm1214

Angiopoietin-related growth factor antagonizes obesity and insulin resistance. / Oike, Yuichi; Akao, Masaki; Yasunaga, Kunio; Yamauchi, Toshimasa; Morisada, Tohru; Ito, Yasuhiro; Urano, Takashi; Kimura, Yoshishige; Kubota, Yoshiaki; Maekawa, Hiromitsu; Miyamoto, Takeshi; Miyata, Keishi; Matsumoto, Shun Ichiro; Sakai, Jura; Nakagata, Naomi; Takeya, Motohiro; Koseki, Haruhiko; Ogawa, Yoshihiro; Kadowaki, Takashi; Suda, Toshio.

In: Nature medicine, Vol. 11, No. 4, 01.04.2005, p. 400-408.

Research output: Contribution to journalArticle

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, SI, 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, vol. 11, no. 4, pp. 400-408. https://doi.org/10.1038/nm1214
Oike Y, Akao M, Yasunaga K, Yamauchi T, Morisada T, Ito Y et al. Angiopoietin-related growth factor antagonizes obesity and insulin resistance. Nature medicine. 2005 Apr 1;11(4):400-408. https://doi.org/10.1038/nm1214
Oike, Yuichi ; Akao, Masaki ; Yasunaga, Kunio ; Yamauchi, Toshimasa ; Morisada, Tohru ; Ito, Yasuhiro ; Urano, Takashi ; Kimura, Yoshishige ; Kubota, Yoshiaki ; Maekawa, Hiromitsu ; Miyamoto, Takeshi ; Miyata, Keishi ; Matsumoto, Shun Ichiro ; Sakai, Jura ; Nakagata, Naomi ; Takeya, Motohiro ; Koseki, Haruhiko ; Ogawa, Yoshihiro ; Kadowaki, Takashi ; Suda, Toshio. / Angiopoietin-related growth factor antagonizes obesity and insulin resistance. In: Nature medicine. 2005 ; Vol. 11, No. 4. pp. 400-408.
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