Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells.
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.
Aas
Vigdis
V
Faculty of Health Sciences, Oslo University College, Oslo, Norway.
Rokling-Andersen
Merethe H
MH
Kase
Eili Tranheim
ET
Thoresen
G Hege
GH
Rustan
Arild C
AC
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
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