title: Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells.
abstract: This study was conducted to evaluate the chronic effects of eicosapentaenoic acid (EPA) on fatty acid and glucose metabolism in human skeletal muscle cells. Uptake of [14C]oleate was increased >2-fold after preincubation of myotubes with 0.6 mM EPA for 24 h, and incorporation into various lipid classes showed that cellular triacylgycerol (TAG) and phospholipids were increased 2- to 3-fold compared with control cells. After exposure to oleic acid (OA), TAG was increased 2-fold. Insulin (100 nM) further increased the incorporation of [14C]oleate into all lipid classes for EPA-treated myotubes. Fatty acid beta-oxidation was unchanged, and complete oxidation (CO2) decreased in EPA-treated cells. Basal glucose transport and oxidation (CO2) were increased 2-fold after EPA, and insulin (100 nM) stimulated glucose transport and oxidation similarly in control and EPA-treated myotubes, whereas these responses to insulin were abolished after OA treatment. Lower concentrations of EPA (0.1 mM) also increased fatty acid and glucose uptake. CD36/FAT (fatty acid transporter) mRNA expression was increased after EPA and OA treatment compared with control cells. Moreover, GLUT1 expression was increased 2.5-fold by EPA, whereas GLUT4 expression was unchanged, and activities of the mitogen-activated protein kinase p38 and extracellular signal-regulated kinase were decreased after treatment with OA compared with EPA. Together, our data show that chronic exposure of myotubes to EPA promotes increased uptake and oxidation of glucose despite a markedly increased fatty acid uptake and synthesis of complex lipids.
authors.affiliation: Faculty of Health Sciences, Oslo University College, Oslo, Norway.
authors.forename: Vigdis
authors.initials: V
authors.lastname: Aas
authors.forename: Merethe H
authors.initials: MH
authors.lastname: Rokling-Andersen
authors.forename: Eili Tranheim
authors.initials: ET
authors.lastname: Kase
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000328:Adult; D018955:CD36 Antigens / Q000235:genetics; D002245:Carbon Dioxide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics; D004075:Diglycerides / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D004075:Diglycerides; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D007328:Insulin; D010743:Phospholipids; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C495680:SLC2A2 protein, human; D014280:Triglycerides; D002245:Carbon Dioxide; D012710:Serum Albumin, Bovine; D019301:Oleic Acid; D006003:Glycogen; D015118:Eicosapentaenoic Acid; D051048:Diacylglycerol O-Acyltransferase; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose