Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis.

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis.
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DOI:
10.1016/j.yhbeh.2014.02.004
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发表时间:
2014-06
影响因子:
3.5
通讯作者:
Clegg, Deborah J.
Clegg, Deborah J.
中科院分区:
医学3区
文献类型:
--
作者:
Davis, Kathryn E.;Carstens, Elizabeth J.;Irani, Boman G.;Gent, Lana M.;Hahner, Lisa M.;Clegg, Deborah J.

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经典的雌激素受体,雌激素受体-α和雌激素受体-β在调节雄性和雌性小鼠的体重和能量平衡方面已被证实,而G蛋白偶联雌激素受体1(GPER)作为能量平衡调节剂的作用仍存在争议。本研究旨在确定GPER基因缺失(GPER KO)是否会改变男性和女性的体重、身体肥胖、食物摄入和能量稳态。缺乏GPER的雄性小鼠从8周龄开始出现中度肥胖和较大的脂肪细胞大小,能量消耗显著减少,但食物摄入或脂肪细胞数量没有减少。相对于WT雌性,雌性GPER KO小鼠的体重增加比雄性GPER KO小鼠晚整整6周。雌性GPER KO小鼠的能量消耗也有所减少,但体脂含量没有显著增加。与其能量消耗的减少一致,GPER KO雄性和雌性动物的两种棕色脂肪产热蛋白显着减少。GPER KO雌性动物在体重差异之前,对瘦素和CCK的摄食抑制作用不如WT雌性动物敏感。此外,在GPER KO小鼠中,卵巢切除术或雌二醇替代对体重没有调节作用。在野生型雌性动物中,雌二醇处理激活磷酸化细胞外信号调节激酶(pERK),但不激活GPER KO雌性动物。首次发现GPER在脂肪细胞中表达,但在脂肪组织的基质部分中没有表达。总之,这些结果提供了新的信息,阐明性二型性GPER功能的发展青春期后的能量平衡。
The classical estrogen receptors, estrogen receptor-α and estrogen receptor-β are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8 weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6 weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but not significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed significant reductions in two brown fat thermogenic proteins. GPER KO females, prior to their divergence in body weight, were less sensitive than WT females to the feeding-inhibitory effects of leptin and CCK. Additionally, body weight was not as modulated by ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but not GPER KO females. For the first time, GPER expression was found in the adipocyte but not the stromal fraction of adipose tissue. Together, these results provide new information elucidating a sexual dimorphism in GPER function in the development of postpubertal energy balance.
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