Salsalate Activates Skeletal Muscle Thermogenesis and Protects Mice from High-Fat Diet Induced Metabolic Dysfunction.
Salsalate Activates Skeletal Muscle Thermogenesis and Protects Mice from High-Fat Diet Induced Metabolic Dysfunction.
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水杨酸激活骨骼肌生热作用并保护小鼠免受高脂肪饮食引起的代谢功能障碍。
DOI：
10.1016/j.ebiom.2017.08.004
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发表时间：
2017-09
期刊：
影响因子：
11.1
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Nie L;Yuan XL;Jiang KT;Jiang YH;Yuan J;Luo L;Cui SW;Sun C
水杨酸盐对改善2型糖尿病患者的高血糖和血脂异常具有有益作用，但其潜在机制尚不清楚。在本研究中，通过给喂食高脂肪饮食的小鼠喂食水杨酸盐，并检查水杨酸盐如何纠正这些肥胖小鼠的代谢功能障碍，我们发现水杨酸盐在不影响食物摄入量的情况下刺激体温并减轻体重增加。我们的研究结果表明，水杨酸盐的应用减少了肝脏和附睾白色脂肪组织（eWAT）的脂质积累，抑制了肝脏糖异生，改善了eWAT中的胰岛素信号转导。此外，水杨酸盐增加了骨骼肌中与葡萄糖和脂肪酸运输和氧化相关的基因的表达。我们的研究结果还表明，水杨酸盐增强了线粒体解偶联和线粒体电子传递的基因表达。此外，水杨酸处理小鼠骨骼肌中的肌磷脂（Sln）和肌浆网Ca2 + atp酶2 （Serca2）增强。综上所述，我们的数据表明，水藻酸盐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轴的骨骼肌产热作用。水杨酸盐改善高脂饮食诱导的肥胖小鼠代谢功能障碍。水杨酸盐通过激活骨骼肌产热来刺激能量消耗。文献表明，水杨酸盐为基础的化合物在治疗肥胖相关代谢综合征中起着有益的作用，而能量消耗的增加被认为是其潜在机制之一。然而，水杨酸盐对能量消耗的靶组织及其作用机制尚不清楚。我们的数据表明，通过激活线粒体解偶联和Sln/Serca2轴，水salsalate刺激高脂肪饮食诱导的肥胖小鼠骨骼肌产热。因此，我们认为骨骼肌产热可能是2型糖尿病患者中水杨酸诱导的能量消耗及其有益代谢作用的原因。
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 Ca2 + 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. Salsalate improves metabolic dysfunction in high-fat diet induced obese mice. Salsalate stimulates energy expenditure by activating skeletal muscle thermogenesis. It has been well documented that salicylate-based compounds play beneficial roles for treating obesity-related metabolic syndromes and enhanced energy expenditure was thought to be one of the underlying mechanisms. However, the tissues targeted by salicylate for energy expenditure and the involved mechanisms are still not clear. Our data show that, by activating mitochondrial uncoupling and the axis of Sln/Serca2, salsalate stimulates skeletal muscle thermogenesis in high-fat diet induced obese mice. Therefore, we suggest skeletal muscle thermogenesis may account for salsalate-induced energy expenditure and its beneficial metabolic effects in type 2 diabetes patients.
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影响因子：
4.6
作者：
Goto-Inoue, Naoko;Yamada, Kenichiro;Inagaki, Akiko;Furuichi, Yasuro;Ogino, Shinya;Manabe, Yasuko;Setou, Mitsutoshi;Fujii, Nobuharu L.
通讯作者：
Fujii, Nobuharu L.
影响因子：
4.8
作者：
Bombardier, Eric;Smith, Ian C.;Tupling, A. Russell
通讯作者：
Tupling, A. Russell
影响因子：
7.3
作者：
Liang, Wen;Verschuren, Lars;van den Hoek, Anita M.
通讯作者：
van den Hoek, Anita M.
影响因子：
4.8
作者：
Odermatt, A;Becker, S;MacLennan, DH
通讯作者：
MacLennan, DH
DOI：
10.1126/science.1215327
发表时间：
2012-05-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hawley SA;Fullerton MD;Ross FA;Schertzer JD;Chevtzoff C;Walker KJ;Peggie MW;Zibrova D;Green KA;Mustard KJ;Kemp BE;Sakamoto K;Steinberg GR;Hardie DG
通讯作者：
Hardie DG