2. Academic Validation
  3. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis

Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis

  • J Biol Chem. 2003 Jan 24;278(4):2461-8. doi: 10.1074/jbc.M209033200.
Toshimasa Yamauchi 1,  Junji Kamon,  Hironori Waki,  Yasushi Imai,  Nobuhiro Shimozawa,  Kyouji Hioki,  Shoko Uchida,  Yusuke Ito,  Keisuke Takakuwa,  Junji Matsui,  Makoto Takata,  Kazuhiro Eto,  Yasuo Terauchi,  Kajuro Komeda,  Masaki Tsunoda,  Koji Murakami,  Yasuyuki Ohnishi,  Takeshi Naitoh,  Kenichi Yamamura,  Yoshito Ueyama,  Philippe Froguel,  Satoshi Kimura,  Ryozo Nagai,  Takashi Kadowaki
Affiliations

Affiliation

  • 1 Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
PMID: 12431986 DOI: 10.1074/jbc.M209033200
Abstract

The adipocyte-derived hormone Adiponectin has been shown to play important roles in the regulation of energy homeostasis and Insulin sensitivity. In this study, we analyzed globular domain Adiponectin (gAd) transgenic (Tg) mice crossed with leptin-deficient ob/ob or apoE-deficient mice. Interestingly, despite an unexpected similar body weight, gAd Tg ob/ob mice showed amelioration of Insulin resistance and beta-cell degranulation as well as diabetes, indicating that globular Adiponectin and Leptin appeared to have both distinct and overlapping functions. Amelioration of diabetes and Insulin resistance was associated with increased expression of molecules involved in fatty acid oxidation such as acyl-CoA oxidase, and molecules involved in energy dissipation such as uncoupling proteins 2 and 3 and increased fatty acid oxidation in skeletal muscle of gAd Tg ob/ob mice. Moreover, despite similar plasma glucose and lipid levels on an apoE-deficient background, gAd Tg apoE-deficient mice showed amelioration of atherosclerosis, which was associated with decreased expression of class A scavenger receptor and tumor necrosis factor alpha. This is the first demonstration that globular Adiponectin can protect against atherosclerosis in vivo. In conclusion, replenishment of globular Adiponectin may provide a novel treatment modality for both type 2 diabetes and atherosclerosis.

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