Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism.
Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism.
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雌激素可保护雄性小鼠免受肥胖并发症的影响，并影响糖皮质激素代谢。
DOI：
10.1038/ijo.2015.102
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Drake AJ
中科院分区：
文献类型：
--
作者：
Dakin RS;Walker BR;Seckl JR;Hadoke PW;Drake AJ
尽管肥胖在女性中的患病率高于男性，但她们在某种程度上免受相关的心脏代谢后果的影响。绝经后心血管疾病风险的增加表明了雌激素的作用。越来越多的证据表明雌性激素对男性体脂和新陈代谢的重要性。我们假设雌激素可以改善肥胖对男性代谢参数的不利影响。雄性和雌性C57Bl/6小鼠从5周龄开始饲喂对照或致肥性（DIO）饲料，直至成年。在13周龄时进行葡萄糖耐量试验。15周龄处死小鼠，收集肝脏和脂肪组织进行基因表达分析。第二组雄性小鼠接受相同的实验设计，在6周时添加雌二醇颗粒植入或假手术。与女性相比，DIO男性有更多的肠系膜脂肪沉积和更严重的血糖、胰岛素和血脂升高。从6周龄开始用雌二醇治疗雄性小鼠，可以防止dio诱导的脂肪组织质量增加和葡萄糖-胰岛素稳态的改变。我们还发现了肝脏和脂肪糖皮质激素代谢酶的转录水平和活性的性别差异。雌激素治疗使dio诱导的糖皮质激素代谢变化模式女性化，使男性与女性相似。因此，DIO诱导了葡萄糖-胰岛素稳态的性别特异性变化，在接受雌激素治疗的男性中，这种变化得到了改善，突出了性类固醇在代谢中的重要性。考虑到在啮齿动物和人类肥胖中观察到外周糖皮质激素代谢的改变，我们的研究结果还表明，糖皮质激素代谢酶的两性二态表达和活性可能在男性和女性对肥胖的不同代谢反应中起作用。
Although the prevalence of obesity is higher among women than men, they are somewhat protected from the associated cardiometabolic consequences. The increase in cardiovascular disease risk seen after the menopause suggests a role for estrogens. There is also growing evidence for the importance of estrogen on body fat and metabolism in males. We hypothesized that that estrogen administration would ameliorate the adverse effects of obesity on metabolic parameters in males. Male and female C57Bl/6 mice were fed control or obesogenic (DIO) diets from 5 weeks of age until adulthood. Glucose tolerance testing was performed at 13 weeks of age. Mice were killed at 15 weeks of age and liver and adipose tissue were collected for analysis of gene expression. A second cohort of male mice underwent the same experimental design with the addition of estradiol pellet implantation or sham surgery at 6 weeks. DIO males had greater mesenteric adipose deposition and more severe increases in plasma glucose, insulin and lipids than females. Treatment of males with estradiol from 6 weeks of age prevented DIO-induced increases in adipose tissue mass and alterations in glucose–insulin homeostasis. We also identified sex differences in the transcript levels and activity of hepatic and adipose glucocorticoid metabolizing enzymes. Estrogen treatment feminized the pattern of DIO-induced changes in glucocorticoid metabolism, rendering males similar to females. Thus, DIO induces sex-specific changes in glucose–insulin homeostasis, which are ameliorated in males treated with estrogen, highlighting the importance of sex steroids in metabolism. Given that altered peripheral glucocorticoid metabolism has been observed in rodent and human obesity, our results also suggest that sexually dimorphic expression and activity of glucocorticoid metabolizing enzymes may have a role in the differential metabolic responses to obesity in males and females.