Androgen Receptor Null Male Mice Develop Late-Onset Obesity Caused by Decreased Energy Expenditure and Lipolytic Activity but Show Normal Insulin Sensitivity With High Adiponectin Secretion

Androgen Receptor Null Male Mice Develop Late-Onset Obesity Caused by Decreased Energy Expenditure and Lipolytic Activity but Show Normal Insulin Sensitivity With High Adiponectin Secretion WuQiang Fan 1 , Toshihiko Yanase 1 , Masatoshi Nomura 1 , Taijiro Okabe 1 , Kiminobu Goto 1 , Takashi Sato 2 , Hirotaka Kawano 2 , Shigeaki Kato 2 and Hajime Nawata 1 1 Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan 2 Institute of Molecular and Cellular Biosciences, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan Address correspondence and reprint requests to Toshihiko Yanase, MD, PhD, Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan. E-mail: yanase{at}intmed3.med.kyushu-u.ac.jp Abstract Androgen receptor (AR) null male mice (AR L−/Y ) revealed late-onset obesity, which was confirmed by computed tomography–based body composition analysis. AR L−/Y mice were euphagic compared with the wild-type male (AR X/Y ) controls, but they were also less dynamic and consumed less oxygen. Transcript profiling indicated that AR L−/Y mice had lower transcripts for the thermogenetic uncoupling protein 1, which was subsequently found to be ligand-dependently activated by AR. We also found enhanced secretion of adiponectin, which is insulin sensitizing, from adipose tissue and a relatively lower expression of peroxisome proliferator–activated receptor-γ in white adipose tissue in comparison to AR X/Y mice. Both factors might explain why the overall insulin sensitivity of AR L−/Y mice remained intact, despite their apparent obesity. The results revealed that AR plays important roles in male metabolism by affecting the energy balance, and it is negative to both adiposity and insulin sensitivity. AR, androgen receptor BAT, brown adipose tissue CT, computed tomography PPAR-γ, peroxisome proliferator–activated receptor-γ UCP, uncoupling protein WAT, white adipose tissue Footnotes Accepted January 6, 2005. Received September 2, 2004. DIABETES