Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
OBJECTIVE
To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men.


METHODS
Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed.


RESULTS
DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production.


CONCLUSIONS
We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.
Movérare-Skrtic
Sofia
S
Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Göteborg, Sweden.
Venken
Katrien
K
Andersson
Niklas
N
Lindberg
Marie K
MK
Svensson
Johan
J
Swanson
Charlotte
C
Vanderschueren
Dirk
D
Oscarsson
Jan
J
Gustafsson
Jan-Ake
JA
Ohlsson
Claes
C
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002153:Calorimetry, Indirect; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D013196:Dihydrotestosterone / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced*; D009919:Orchiectomy / Q000009:adverse effects*; D011944:Receptors, Androgen / Q000502:physiology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D008076:Cholesterol, HDL; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D014280:Triglycerides; D013196:Dihydrotestosterone; D002784:Cholesterol