Dihydrotestosterone Treatment Results in Obesity and Altered Lipid Metabolism in Orchidectomized Mice

Authors

  • Sofia Movérare-Skrtic,

    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • Katrien Venken,

    1. Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Niklas Andersson,

    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • Marie K. Lindberg,

    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • Johan Svensson,

    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • Charlotte Swanson,

    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • Dirk Vanderschueren,

    1. Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium
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  • Jan Oscarsson,

    1. Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
    2. AstraZeneca Research and Development, Mölndal, Sweden
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  • Jan-Åke Gustafsson,

    1. Department of Biosciences at Novum and Department of Medical Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden.
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  • Claes Ohlsson

    Corresponding author
    1. Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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  • The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Department of Internal Medicine, Division of Endocrinology, Gröna Stråket 8, 41345 Gothenburg, Sweden. E-mail: claes.ohlsson@medic.gu.se

Abstract

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 α stimulation results in reduced fat mass in men.

Research Methods and Procedures: Orchidectomized mice were treated with the non-aromatizable androgen 5α-dihydrotestosterone (DHT), 17β-estradiol, or vehicle. VO2, 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 high-density 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.

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