title: Marine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure.
abstract: Insulin resistance is an important risk factor for the development of several cardiac pathologies, thus advocating strategies for restoring insulin sensitivity of the heart in these conditions. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), have been shown to improve insulin sensitivity in insulin-sensitive tissues, but their direct effect on insulin signaling and metabolic parameters in the myocardium has not been reported previously. The aim of this study was therefore to examine the ability of EPA and DHA to prevent insulin resistance in isolated rat cardiomyocytes. Primary rat cardiomyocytes were made insulin resistant by 48 h incubation in high insulin (HI) medium. Parallel incubations were supplemented by 200 μM EPA or DHA. Addition of EPA or DHA to the medium prevented the induction of insulin resistance in cardiomyocytes by preserving the phosphorylation state of key proteins in the insulin signaling cascade and by preventing persistent relocation of fatty acid transporter CD36 to the sarcolemma. Only cardiomyocytes incubated in the presence of EPA, however, exhibited improvements in glucose and fatty acid uptake and cell shortening. We conclude that ω-3 PUFAs protect metabolic and functional properties of cardiomyocytes subjected to insulin resistance-evoking conditions.
authors.affiliation: Cardiovascular Research Group, Department of Medical Biology, Health Sciences Faculty, UiT The Arctic University of Norway, Tromsø, Norway; veronika.franekova@uit.no.
authors.forename: Veronika
authors.initials: V
authors.lastname: Franekova
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Angin
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and.
authors.forename: Nicole T H
authors.initials: NT
authors.lastname: Hoebers
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and.
authors.forename: Will A
authors.initials: WA
authors.lastname: Coumans
authors.affiliation: Bioceros BV, Utrecht, the Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Simons
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and.
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; and.
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.affiliation: Cardiovascular Research Group, Department of Medical Biology, Health Sciences Faculty, UiT The Arctic University of Norway, Tromsø, Norway;
authors.forename: Terje S
authors.initials: TS
authors.lastname: Larsen
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D021381:Protein Transport; D011917:Rats, Inbred Lew; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D002316:Cardiotonic Agents; C008132:Cd36 protein, rat; D007328:Insulin; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D005947:Glucose
keywords: CD36; adipose triglyceride lipase; cardiac metabolism; insulin resistance; omega-3 PUFAs; sarcomere shortening