Movérare-Skrtic Sofia, Venken Katrien, Andersson Niklas, Lindberg Marie K, Svensson Johan, Swanson Charlotte, Vanderschueren Dirk, Oscarsson Jan, Gustafsson Jan-Ake, Ohlsson Claes
Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Göteborg, Sweden.
Obesity (Silver Spring). 2006 Apr;14(4):662-72. doi: 10.1038/oby.2006.75.
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.
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.
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.
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.
确定雄激素受体(AR)激活在脂肪组织代谢中的作用。性类固醇是男性脂肪组织代谢的重要调节因子。雄激素可能通过刺激AR直接调节男性脂肪组织代谢,也可能通过将雄激素芳香化为雌激素,然后刺激雌激素受体间接调节。先前的研究表明,刺激雌激素受体α会导致男性脂肪量减少。
对去势小鼠用不可芳香化的雄激素5α-二氢睾酮(DHT)、17β-雌二醇或赋形剂进行处理。测量耗氧量(Vo₂)、二氧化碳排出量(Vco₂)、静息代谢率、运动活动和食物消耗量。此外,分析肝脏基因表达的变化。
DHT处理导致肥胖,伴有能量消耗和脂肪氧化减少。相比之下,DHT不影响食物消耗量或运动活动。此外,DHT处理导致高密度脂蛋白胆固醇和甘油三酯水平升高,同时7α-羟化酶基因表达明显降低,表明胆汁酸生成减少。
我们表明,AR激活会导致去势小鼠肥胖和脂质代谢改变。有人可能推测,AR拮抗剂可能对治疗男性肥胖有用。