title: 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.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. oike@sc.itc.keio.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Masaki
authors.initials: M
authors.lastname: Akao
authors.forename: Kunio
authors.initials: K
authors.lastname: Yasunaga
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Tohru
authors.initials: T
authors.lastname: Morisada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Urano
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Kimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Maekawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Juro
authors.initials: J
authors.lastname: Sakai
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001685:Biological Factors / Q000235:genetics / Q000502:physiology*; D004041:Dietary Fats; D004734:Energy Metabolism; D007333:Insulin Resistance; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009765:Obesity / Q000517:prevention & control*
chemical_list: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C477602:Angptl6 protein, mouse; D001685:Biological Factors; D004041:Dietary Fats