Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

• Klíčová slova
• Mitochondrial respiration, Mitochondrial uncoupling, PPARδ, PPARδ agonist, Saturated fatty acid, Skeletal muscle cells, Unsaturated fatty acids,
• MeSH
• buněčná smrt účinky léků   MeSH
• buněčné linie MeSH
• dietní tuky nenasycené farmakologie   MeSH
• kosterní svaly účinky léků   metabolismus   MeSH
• kyselina palmitová toxicita   MeSH
• myši MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• sulfony farmakologie   MeSH
• svalové buňky účinky léků   metabolismus   MeSH
• thiazoly farmakologie   MeSH
• thiofeny farmakologie   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dietní tuky nenasycené MeSH
• GSK0660 MeSH Prohlížeč
• GW 501516 MeSH Prohlížeč
• kyselina palmitová MeSH
• Ppard protein, mouse MeSH Prohlížeč
• receptory cytoplazmatické a nukleární MeSH
• sulfony MeSH
• thiazoly MeSH
• thiofeny MeSH