Effect of estrodiol on leptin receptors expression in regulating fat distribution and adipocyte genesis

Abstract

Objective: To examine how estradiol influence fat distribution and adipocyte genesis through regulating leptin function.

Design and methods: We randomized female SD rats into ovariectomy and sham group. After 14 weeks, we examined leptin receptor expression in perigenital, mesenteric and subcutaneous adipose tissues and leptin in serum. We further introduced mesenchymal stem cells (MSCs) to figure out the effect of 17-β estradiol on expression of leptin receptors (OBRb and OBRa), leptin and PPARγ2.

Results: Weight and Lee’s index was both significantly higher in ovariectomized group than sham group (p < 0.001). The interaction of serum E₂ and leptin was negatively correlated with body weight. Expression of leptin receptor protein was extremely upregulated in ovariectomized group in perigenital and mesenteric fat. Both estradiol and leptin upregulated mRNA expression of OBRb, and created a dose-dependent decreasing manner in MSCs. Higher doses of estradiol (10⁻⁷–10⁻⁵ M) inhibited adipogenic markers mRNA expression of leptin and PPARγ2, but low doses promoted leptin expression.

Conclusions: In ovariectomized rats, low level of serum estradiol may change body composition and promote adipocyte genesis through affecting leptin function.

Chinese abstract

目的：研究雌二醇如何通过调节瘦素功能影响脂肪分布和脂肪细胞的产生。

设计和方法:雌性SD大鼠随机分成卵巢切除组和虚假手术组。14周后，检测生殖器周围，肠系膜及皮下脂肪组织瘦素受体的表达和血清中的瘦素水平。我们进一步研究间充质干细胞(msc)，检测17-β雌二醇对瘦素受体(OBRb和OBRa)，瘦素和PPARg2表达的影响。

结果:体重和李氏指数卵巢切除组显著高于虚假手术组(p<0.001)。血清E2和瘦素与体重成负相关。瘦素受体蛋白质的表达在切除卵巢组的生殖器周围及肠系膜脂肪的表达明显上调。雌二醇和瘦素均上调OBRb mRNA的表达，致MSCs中的剂量依赖性降低的方式。高剂量的雌二醇(10^-7–10^-5M)抑制瘦素和PPARg2脂肪生成标志物mRNA的表达，低剂量促进瘦素表达。

结论：在切除卵巢的老鼠，血清低水平的雌二醇可能通过影响瘦素的功能来改变身体组成，促进脂肪细胞生成。

• Body mass index
• estrogens
• leptin
• menopause

Acknowledgements

Many thanks to Professor Deying Kang (Department of Clinical Epidemiology, Hospital of West China, Sichuan University) for giving advices on the statistical analysis. Many thanks to Tingting Li, Jing Zhan and Dan Shan for sample and data collection.

Declaration of interest

This work was supported by the National Natural Science Foundation of China (Dr. Liangzhi Xu, Principal Investigator, Project No. 81070464) and Research Fund for the Doctoral Program of Higher Education, China (Dr. Liangzhi Xu, Principal Investigator, Project No. 20100181110007). All authors declared there is no relevant conflict of interest.