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标题：Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity
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作者：Wei Hu ; Jacek Bielawski ; Fahumiya Samad 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：9
页码：1852-1862
DOI：10.1194/jlr.M800635-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Studies in skeletal muscle demonstrate that elevation of plasma FFAs increases the sphingolipid ceramide. We aimed to determine the impact of FFA oversupply on total sphingolipid profiles in a skeletal muscle model. C2C12 myotubes were treated with palmitate (PAL). Lipidomics analysis revealed pleiotropic effects of PAL on cell sphingolipids not limited to ceramides. ¹³C labeling demonstrated that PAL activated several branches of sphingolipid synthesis by distinct mechanisms. Intriguingly, PAL increased sphingosine-1-phosphate independently of de novo synthesis. Quantitative real-time PCR demonstrated that PAL increased sphingosine kinase 1 (SK1) mRNA by approximately 4-fold. This was accompanied by a 2.3-fold increase in sphingosine kinase enzyme activity. This upregulation did not occur upon treatment with oleate, suggesting some level of specificity for PAL. These findings were recapitulated in the diet-induced obesity mouse model, in which high-fat feeding increased SK1 message in skeletal muscle over 2.3-fold. These data suggest that the impact of elevated FFA on sphingolipids reaches beyond ceramides and de novo sphingolipid synthesis. Moreover, these findings identify PAL as a novel regulatory stimulus for SK1.
关键词：free fatty acid ; sphingolipid ; ceramide ; skeletal muscle ; insulin resistance ; diabetes ; obesity ; lipotoxicity