Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice

Sofia Movérare-Skrtic, Katrien Venken, Niklas Andersson, Marie K. Lindberg, Johan Svensson, Charlotte Swanson, Dirk Vanderschueren, Jan Oscarsson, Jan Åke Gustafsson, Claes Ohlsson

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Objectives: 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 a stimulation results in reduced fat mass in men. Research Methods and Procedures: Orchidectomized mice were treated with the non-aromatizable androgen 5αdihydrotestosterone (DHT), 17β-estradiol, or vehicle. VO 2, VCO2, 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 highdensity lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7α-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.

Original languageEnglish (US)
Pages (from-to)662-672
Number of pages11
JournalObesity
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Androgen receptor
  • Aromatization
  • Estrogen
  • Microarray
  • Transgenic

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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