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Endocrinology Vol. 144, No. 1 253-259
Copyright © 2003 by The Endocrine Society


ARTICLE

Dehydroepiandrosterone Down-Regulates the Expression of Peroxisome Proliferator-Activated Receptor {gamma} in Adipocytes

Kazuo Kajita, Tatsuo Ishizuka, Tomoatsu Mune, Atsushi Miura, Masayoshi Ishizawa, Yoshinori Kanoh, Yasunori Kawai, Yoshiyuki Natsume and Keigo Yasuda

The Third Department of Internal Medicine (K.K., T.M., A.M., M.I., Y.Kan., Y.Kaw., Y.N., K.Y.) and Department of General Medicine (T.I.), Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500-8705, Japan

Address all correspondence and requests for reprints to: Tatsuo Ishizuka, Department of General Medicine, Gifu University School of Medicine, Tsukasa-Machi 40, Gifu 500-8705, Japan. E-mail: tishizuk-gif{at}umin.ac.jp.

Dehydroepiandrosterone (DHEA) is expected to have a weight-reducing effect. In this study, we evaluated the effect of DHEA on genetically obese Otsuka Long Evans Fatty rats (OLETF) compared with Long-Evans Tokushima rats (LETO) as control. Feeding with 0.4% DHEA-containing food for 2 wk reduced the weight of sc, epididymal, and perirenal adipose tissue in association with decreased plasma leptin levels in OLETF. Adipose tissue from OLETF showed increased expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) protein, which was prevented by DHEA treatment. Further, we examined the effect of DHEA on PPAR{gamma} in primary cultured adipocytes and monolayer adipocytes differentiated from rat preadipocytes. PPAR{gamma} protein level was decreased in a time- and concentration-dependent manner, and DHEA significantly reduced mRNA levels of PPAR{gamma}, adipocyte lipid-binding protein, and sterol regulatory element-binding protein, but not CCAAT/enhancer binding protein {alpha}. DHEA-sulfate also reduced the PPAR{gamma} protein, but dexamethasone, testosterone, or androstenedione did not alter its expression. In addition, treatment with DHEA for 5 d reduced the triglyceride content in monolayer adipocytes. These results suggest that DHEA down-regulates adiposity through the reduction of PPAR{gamma} in adipocytes.




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