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Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats

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Abstract

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.

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Acknowledgments

The authors declared no conflict of interest. This work is supported by National Natural Science Foundation of P. R. China (No: 30700282) and Guangdong Natural Science Foundation (No: 06021361). We also gratefully acknowledge the professional assistance of Dr. Panwei Mu and Prof. Lin Li in the third affiliated hospital of Sun Yat-Sen University. We acknowledge Prof. Chiu Shuen Hui (Indiana University-Purdue University Indianapolis) for reading and correcting the manuscript.

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  1. Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou, 510080, People’s Republic of China

    JinWen Xu, QiuLing Xiang, GuiPing Lin, XiaoDong Fu, KeWen Zhou, Ping Jiang, ShuHui Zheng & TingHuai Wang

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JinWen Xu, QiuLing Xiang contributed equal to this work.

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Xu, J., Xiang, Q., Lin, G. et al. Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats. Mol Biol Rep 39, 8177–8185 (2012). https://doi.org/10.1007/s11033-012-1665-1

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