Shen Yang, Zhao Yuyan, Yuan Lizhi, Yi Wei, Zhao Rui, Yi Qianru, Yong Tongwu
Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
Department of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People's Republic of China.
Acta Histochem. 2014 Jan;116(1):158-66. doi: 10.1016/j.acthis.2013.06.004. Epub 2013 Aug 2.
Secreted protein acidic and rich in cysteine (SPARC) is a secretory multifunctional matricellular glycoprotein. High circulating levels of SPARC have been reported to be associated with obesity and insulin resistance. The aim of the present study was to investigate whether SPARC induces insulin resistance and mitochondrial dysfunction in adipocytes. Our results showed that feeding high fat diet to rats for 12 weeks significantly increased SPARC expression in adipose tissues at both mRNA and protein levels. Moreover, SPARC overexpression in stably transfected 3T3-L1 cells induced insulin resistance and mitochondrial dysfunction, as evidenced by inhibition of insulin-stimulated glucose transport, lower ATP synthesis and mitochondrial membrane potential, reduced expression of glucose transporter 4 (GLUT4), and increased levels of reactive oxygen species (ROS) in mature adipocytes. Finally, overexpression of SPARC also modulated the expression levels of several inflammatory cytokines, which play important roles in insulin resistance, glucose and lipid metabolism during adipogenesis. In conclusion, our data suggest that SPARC is involved in obesity-induced adipose insulin resistance and may serve as a potential target in the treatment of obesity and obesity-related insulin resistance.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种分泌型多功能基质细胞糖蛋白。据报道，循环中SPARC的高含量与肥胖和胰岛素抵抗有关。本研究的目的是调查SPARC是否会诱导脂肪细胞中的胰岛素抵抗和线粒体功能障碍。我们的结果表明，给大鼠喂食高脂肪饮食12周会显著增加脂肪组织中SPARC在mRNA和蛋白质水平上的表达。此外，在稳定转染的3T3-L1细胞中过表达SPARC会诱导胰岛素抵抗和线粒体功能障碍，这在成熟脂肪细胞中表现为胰岛素刺激的葡萄糖转运受到抑制、ATP合成和线粒体膜电位降低、葡萄糖转运蛋白4（GLUT4）的表达减少以及活性氧（ROS）水平升高。最后，SPARC的过表达还调节了几种炎症细胞因子的表达水平，这些细胞因子在脂肪生成过程中的胰岛素抵抗、葡萄糖和脂质代谢中起重要作用。总之，我们的数据表明SPARC参与肥胖诱导的脂肪胰岛素抵抗，可能成为治疗肥胖和肥胖相关胰岛素抵抗的潜在靶点。
