title: N-3PUFA differentially modulate palmitate-induced lipotoxicity through alterations of its metabolism in C2C12 muscle cells.
abstract: 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.
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France. Electronic address: alexandre.pinel@clermont.inra.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pinel
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France. Electronic address: jean-paul.rigaudiere@clermont.inra.fr.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Rigaudière
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France. Electronic address: brigitte.laillet@clermont.inra.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laillet
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Plateforme d'Exploration du Métabolisme, 63122 Saint-Genès-Champanelle, France. Electronic address: corinne.pouyet@clermont.inra.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pouyet
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France. Electronic address: corinne.malpuech-brugere@udamail.fr.
authors.forename: Corinne
authors.initials: C
authors.lastname: Malpuech-Brugère
authors.affiliation: Institut Cochin, Département d'Endocrinologie, Métabolisme and Diabète, U1016 Inserm/UMR8104 CNRS/UMR-S8104, bâtiment Faculté, 3(ème) étage, Salle 3012A, 24 rue du faubourg Saint Jacques, 75014 Paris, France. Electronic address: carina.prip-buus@inserm.fr.
authors.forename: Carina
authors.initials: C
authors.lastname: Prip-Buus
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France; INRA, UMR 1397, Laboratoire CarMeN, Université Lyon 1, INSERM U1060, INSA de Lyon, Université Lyon-Sud Rockefeller et Charles Merieux, Lyon, France. Electronic address: beatrice.morio@clermont.inra.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Morio
authors.affiliation: Institut National de la Recherche Agronomique, UMR1019 Nutrition Humaine, Laboratoire de Nutrition Humaine, Université d'Auvergne, CRNH, 58 rue Montalembert BP321, 63009 Clermont Ferrand CEDEX 1, France. Electronic address: frederic.capel@clermont.inra.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Capel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D007527:Isoenzymes / Q000502:physiology; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010168:Palmitates / Q000633:toxicity*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D000074121:Protein Kinase C-theta
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007527:Isoenzymes; D010168:Palmitates; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D005947:Glucose
keywords: DHA; EPA; Fatty acid metabolism; Insulin resistance; Omega-3 fatty acids; Palmitate