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雌激素通过瘦素信号通路途径调节脂肪细胞代谢生成

Estrogen regulate adipocyte metabolism through leptin signaling pathway

中文摘要英文摘要

目的:探讨雌激素是否是通过瘦素相关信号通路对女性形体改变产生影响。方法:二月龄雌性SD大鼠随机为去势组及假手术组,术后14周收集生殖器周围脂肪、内脏脂肪和皮下脂肪,并分别检测瘦素受体表达,同时通过17-β雌二醇及瘦素对脂肪细胞前体细胞(MSCs)进行干预,检验瘦素受体亚型、瘦素表达及成脂分化的指标PPARγ的变化。结果:通过对造模期间大鼠体重的每周监测,发现去势组体重增长及术后14周Lee's指数均明显高于假手术组(P<0.001)。瘦素受体在去势组的脂肪组织中表达显著增加,内脏脂肪中尤为明显。体外实验显示,随着瘦素和雌激素浓度的增加,MSCs上瘦素长形受体和短受体的表达均随之下降;随雌激素浓度的增加,MSCs中瘦素表达呈下降趋势,同时,MSCs中PPARγ表达也受到抑制。结论:在低雌激素的影响下,去势后大鼠发生类似绝经后女性样的形体改变,高浓度雌激素可抑制大鼠间充质干细胞向脂肪细胞分化,雌激素对瘦素及瘦素受体的影响可能是绝经后女性体型变化发生变化的原因。

Postmenopausal women often present obvious body composition changes under the absence of estrogen, including overweight, obesity and android-like body fat distribution, therefore poses serious threaten for women's health. Although the intimate relationship between estrogen and body appearance have been noticed, mechanism remains unclear. We assumed that estrogen may regulate fat distribution through affecting leptin signal pathway, which has been shown playing major role in energy homeostasis. To test this hypothesis, we randomized female SD rat into ovariectomy (OVX) and sham group, and then collected adipose tissue around genital, retroperitoneal and subcutaneous after 14 week. Leptin receptor expression in adipose tissue was measured by western blot. Results indicated that leptin receptor were significantly down-regulated in ovariectomy group, especially in fat around genital. Weight changes were observed every week, repeated measures analysis of variance showed that OVX group has higher weight gain compared with sham group during the 3 month (P< 0.001), and so does the Lee's index (P< 0.001), which were calculated at the end of the study. We further used mesenchymal stem cells (MSCs), the progenitor of Adipocytes as an in vitro model to figure out the effect of estrogen on leptin receptor expression. After MSCs were treated by increasingconcentration of 17-βestradiol and letpin respectively, QPCR were used to test the mRNA expression of leptin receptor subtype, OBRb (long form) and OBRa (short form). Negative correlation was noticed between estrogen concentration and leptin receptor subtype expression. Similar tendency were also observed in leptin treatment group. Besides, the expression of leptin in MSCs was degrading accompaied with increasing concentration of estrogen, and PPARγ, the indicator of adipogenisis, was also supressed under treatment of estrogen. Estrogen may act on leptin receptor expression to influence the body composition in postmenopausal women. And the similar molecular mechanism of estrogen and leptin shows that these two hormones probably have synergistic effects on energy metabolism.

庄静、许良智、詹晶、程萌、牟丽、李婷婷、许文明、李文娟、陈焱

基础医学生理学生物化学

妇产科学雌激素瘦素瘦素受脂肪间充质干细胞

GynecologyEstrogenLeptinLeptin receptorAdiposeMesenchymal stem cells

庄静,许良智,詹晶,程萌,牟丽,李婷婷,许文明,李文娟,陈焱.雌激素通过瘦素信号通路途径调节脂肪细胞代谢生成[EB/OL].(2012-09-19)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/201209-210.点此复制

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