title: Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells.
abstract: Here we report that in skeletal muscle cells the contribution to insulin resistance and inflammation of two common dietary long-chain fatty acids depends on the channeling of these lipids to distinct cellular metabolic fates. Exposure of cells to the saturated fatty acid palmitate led to enhanced diacylglycerol levels and the consequent activation of the protein kinase C/nuclear factor kappaB pathway, finally resulting in enhanced interleukin 6 secretion and down-regulation of the expression of genes involved in the control of the oxidative capacity of skeletal muscle (peroxisome proliferator-activated receptor (PPAR)gamma-coactivator 1alpha) and triglyceride synthesis (acyl-coenzyme A: diacylglycerol acyltransferase 2). In contrast, exposure to the monounsaturated fatty acid oleate did not lead to these changes. Interestingly, co-incubation of cells with palmitate and oleate reversed both inflammation and impairment of insulin signaling by channeling palmitate into triglycerides and by up-regulating the expression of genes involved in mitochondrial beta-oxidation, thus reducing its incorporation into diacylglycerol. Our findings support a model of cellular lipid metabolism in which oleate protects against palmitate-induced inflammation and insulin resistance in skeletal muscle cells by promoting triglyceride accumulation and mitochondrial beta-oxidation through PPARalpha- and protein kinase A-dependent mechanisms.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Coll
authors.forename: Elena
authors.initials: E
authors.lastname: Eyre
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Calvo
authors.forename: Xavier
authors.initials: X
authors.lastname: Palomer
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Merlos
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Laguna
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D015536:Down-Regulation; D007249:Inflammation; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology*; D019301:Oleic Acid / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010168:Palmitates / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004075:Diglycerides; D015850:Interleukin-6; D010168:Palmitates; D014280:Triglycerides; D019301:Oleic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D010100:Oxygen