Androgen receptor (AR) null male mice (ARL-/Y) revealed late-onset obesity, which was confirmed by computed tomography-based body composition analysis. ARL-/Y mice were euphagic compared with the wild-type male (ARX/Y) controls, but they were also less dynamic and consumed less oxygen. Transcript profiling indicated that ARL-/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 ARX/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.
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