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 (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-gamma 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.
Fan
WuQiang
W
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582 Japan.
Yanase
Toshihiko
T
Nomura
Masatoshi
M
Okabe
Taijiro
T
Goto
Kiminobu
K
Sato
Takashi
T
Kawano
Hirotaka
H
Kato
Shigeaki
S
Nawata
Hajime
H
D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging; D000818:Animals; D001835:Body Weight; D002352:Carrier Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007473:Ion Channels; D008066:Lipolysis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010101:Oxygen Consumption; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D000071256:Uncoupling Protein 1
D052242:Adiponectin; D002352:Carrier Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011944:Receptors, Androgen; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1