N − 3PUFA differentially modulate palmitate-induced lipotoxicity through alterations of its metabolism in C2C12 muscle cells

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• 作者：Alexandre Pinel^a ; ^{alexandre.pinel@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author} ; Jean-Paul Rigaudiè ; re^a ; ^{jean-paul.rigaudiere@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author} ; Brigitte Laillet^a ; ^{brigitte.laillet@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author} ; Corinne Pouyet^b ; ^{corinne.pouyet@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author} ; Corinne Malpuech-Brugè ; re^a ; ^{corinne.malpuech-brugere@udamail.fr" class="auth_mail" title="E-mail the corresponding author} ; Carina Prip-Buus^c ; ^{carina.prip-buus@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Bé ; atrice Morio^a ; ^d ; ^{beatrice.morio@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author} ; Fré ; dé ; ric Capel^a ; ^{frederic.capel@clermont.inra.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：2-NBDG ; fluorescent glucose analog ; ALA ; alpha-linolenic acid ; AMPK ; AMP-activated protein kinase ; AS160 ; AKT substrate of 160  ; kDa ; cpt1 ; carnitine palmitoyltransferase 1 ; DMEM ; Dulbecco's modified eagle medium ; DHA ; docosahexaenoic acid ; DPH ; diphenyl-hexatriene ; ECL ; enhanced chemiluminescence ; EPA ; eicosapentaenoic acid ; EtOH ; ethanol ; FAT ; fatty acid transporter ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase ; GLUT ; glucose transporter ; hprt ; hypoxanthine guanine phosphoribosyltransfer
• 刊名：Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：1861
• 期：1
• 页码：12-20
• 全文大小：916 K

文摘

Excessive energy intake leads to fat overload and the formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate (PAL), thus promoting insulin resistance (IR) in skeletal muscle. N − 3 polyunsaturated fatty acids (n − 3PUFA) may prevent lipotoxicity and IR. The purpose of this study was to examine the differential effects of n − 3PUFA on fatty acid metabolism and insulin sensitivity in muscle cells. C2C12 myotubes were treated with 500 μM of PAL without or with 50 μM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16 h. PAL decreased insulin-dependent AKT activation and glucose uptake and increased the synthesis of ceramides and diglycerides (DG) derivatives, leading to protein kinase Cθ activation. EPA and DHA, but not ALA, prevented PAL-decreased AKT activation but glucose uptake was restored to control values by all n − 3PUFA vs. PAL. Total DG and ceramide contents were decreased by all n − 3PUFA, but only EPA and DHA increased PAL β-oxidation, decreased PAL incorporation into DG and reduced protein kinase Cθ activation. EPA and DHA emerge as better candidates than ALA to improve fatty acid metabolism in skeletal muscle cells, notably via their ability to increase mitochondrial β-oxidation.