Abstract
Fenofibrate is a peroxisome proliferator-activated receptor-α that has been clinically used to treat dyslipidemia and insulin resistance. To better understand the molecular mechanisms underlying fenofibrate action, we investigated whether fenofibrate affects serum levels of vaspin, an adipocytokine that has recently been shown to link obesity and insulin resistance. Fenofibrate treatment significantly increased serum vaspin levels of dyslipidemic patients, which correlated with reduced body weight and increased insulin sensitivity. To elucidate the biochemical mechanisms of fenofibrate action, we investigated the effect of fenofibrate on vaspin mRNA and protein expressions in obese rats. Fenofibrate greatly increased vaspin mRNA and protein levels in visceral adipose tissue consisting of retroperitoneal, mesenteric, and periepididymal adipose tissue but not in the subcutaneous adipose tissue, which correlated with increased serum vaspin levels and increased insulin sensitivity in obese rats. Consistent with a direct effect on vaspin expression, fenofibrate treatment significantly increased the mRNA and protein expression levels of vaspin in 3T3-L1 adipocytes. Together, our results demonstrate for the first time that fenofibrate upregulates vaspin expression in dyslipidemic human subjects and suggest that upregulation of vaspin expression in adipocytes may provide a mechanism by which fenofibrate improves insulin sensitivity in dyslipidemic patients.
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Acknowledgments
This study was supported by the national TCM clinical research base of special foundation (No. JDZX2012005) and the Ministry of Education Foundation of Anhui Province (No. KJ2011A161), PR China. We thank Wenping Wang, Liping Wang, Qihuan Lü, and Xiaohui Zhou for their scientific input and assistance in various aspects of these studies.
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The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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Mingwei Chen and Datong Deng have contributed equally to this study.
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Chen, M., Deng, D., Fang, Z. et al. Fenofibrate increases serum vaspin by upregulating its expression in adipose tissue. Endocrine 45, 409–421 (2014). https://doi.org/10.1007/s12020-013-0023-y
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DOI: https://doi.org/10.1007/s12020-013-0023-y