Department of Endocrinology and Metabolic Diseases, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
Key Laboratory for Neuroregeneration of Jiangsu Province, Ministry of Education, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, China.
EBioMedicine. 2017 Sep;23:136-145. doi: 10.1016/j.ebiom.2017.08.004. Epub 2017 Aug 4.
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT. In addition, salsalate increased the expression of genes related to glucose and fatty acid transport and oxidation in skeletal muscle. Our results also showed that expression of genes in mitochondrial uncoupling and mitochondrial electron transport are strengthened by salsalate. Moreover, sarcolipin (Sln) and sarcoplasmic reticulum Ca ATPase 2 (Serca2) in skeletal muscle were enhanced in salsalate-treated mice. Together, our data suggest that the beneficial metabolic effects of salsalate may depend, at least in part, on skeletal muscle thermogenesis via activation of mitochondrial uncoupling and the axis of Sln/Serca2a.
柳氮磺吡啶对改善 2 型糖尿病患者的高血糖和血脂异常具有有益作用，但作用机制尚不清楚。本研究通过给予高脂肪饮食喂养的小鼠柳氮磺吡啶，并观察柳氮磺吡啶如何纠正这些肥胖小鼠的代谢功能障碍，发现柳氮磺吡啶可刺激体温升高，减轻体重增加，而不影响食物摄入。我们的结果表明，柳氮磺吡啶应用可减少肝脏和附睾白色脂肪组织（eWAT）中的脂质积累，抑制肝糖异生，并改善 eWAT 中的胰岛素信号转导。此外，柳氮磺吡啶增加了骨骼肌中与葡萄糖和脂肪酸转运及氧化相关的基因的表达。我们的结果还表明，柳氮磺吡啶增强了线粒体解偶联和线粒体电子传递相关基因的表达。此外，骨骼肌中的肌浆球蛋白（Sln）和肌浆网 Ca2+-ATP 酶 2（Serca2）在柳氮磺吡啶处理的小鼠中增强。总之，我们的数据表明，柳氮磺吡啶的有益代谢作用可能至少部分依赖于通过激活线粒体解偶联和 Sln/Serca2a 轴来促进骨骼肌产热。
