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J. Biol. Chem., Vol. 277, Issue 29, 25863-25866, July 19, 2002
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§¶,§,§,
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From the The adipocyte-derived hormone
adiponectin has been proposed to play important roles in the regulation
of energy homeostasis and insulin sensitivity, and it has been reported
to exhibit putative antiatherogenic properties in vitro. In
this study we generated adiponectin-deficient mice to directly
investigate whether adiponectin has a physiological protective role
against diabetes and atherosclerosis in vivo. Heterozygous
adiponectin-deficient (adipo+/ Department of Metabolic Diseases, Graduate
School of Medicine, University of Tokyo, Tokyo 113-8655, § Core Research for Evolutional Science and Technology
(CREST) of Japan Science and Technology Corporation, Saitama
332-0012, Third Department of Internal Medicine, Toho University
School of Medicine, Ohashi Hospital, Tokyo 153-0044, ¶¶ Lille Institute of Biology-CNRS 8090 and Lille
Pasteur Institute, 59000 Lille, France, ** Department of
Cardiovascular Diseases, Graduate School of Medicine, University of
Tokyo, Tokyo 113-8655, ¶ Department of Cell Biology, Japanese
Foundation for Cancer Research-Cancer Institute, Tokyo 170-8455, and
§§ Department of Molecular Genetics, Tohoku
University School of Medicine, Sendai 980-8575, Japan
) mice showed
mild insulin resistance, while homozygous adiponectin-deficient (adipo/) mice showed moderate insulin
resistance with glucose intolerance despite body weight gain similar to
that of wild-type mice. Moreover, adipo/
mice showed 2-fold more neointimal formation in response to external vascular cuff injury than wild-type mice (p = 0.01).
This study provides the first direct evidence that adiponectin plays a
protective role against insulin resistance and atherosclerosis in
vivo.
To whom correspondence should be addressed: Dept. of Metabolic
Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: 81-3-5800-8818; Fax:
81-3-5689-7209; E-mail: kadowaki-3im@h.u-tokyo.ac.jp.
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