Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
Journal article, 2006
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. RESEARCH METHODS AND PROCEDURES: 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. DISCUSSION: 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.
blood
physiology
Indirect
drug effects
Mice
Androgen
Mice
Triglycerides
Receptors
Mice
Cholesterol
pharmacology
Knockout
adverse effects
Liver
metabolism
Male
drug effects
drug effects
Animals
Body Weight
blood
Calorimetry
blood
Cholesterol
drug effects
Gene Expression Regulation
Estrogen Receptor alpha
metabolism
metabolism
Dihydrotestosterone
Lipid Metabolism
metabolism
genetics
Adiposity
Orchiectomy
Obesity
chemically induced
drug effects
HDL
Inbred C57BL
Author
Sofia Movérare-Skrtic
University of Gothenburg
Katrien Venken
Niklas Andersson
University of Gothenburg
Marie K Lindberg
University of Gothenburg
Johan Svensson
University of Gothenburg
Charlotte Swanson
University of Gothenburg
Dirk Vanderschueren
Jan Oscarsson
University of Gothenburg
Jan-Ake Gustafsson
Claes Ohlsson
University of Gothenburg
Obesity
1930-7381 (ISSN)
Vol. 14 4 662-72Subject Categories
Endocrinology and Diabetes
Physiology
Cardiac and Cardiovascular Systems
DOI
10.1038/oby.2006.75
PubMed
16741268