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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Adult
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CD36 Antigens / genetics
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Carbon Dioxide / metabolism
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Cell Differentiation / drug effects
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Cells, Cultured
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Diacylglycerol O-Acyltransferase / genetics
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Diglycerides / metabolism
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Eicosapentaenoic Acid / pharmacology*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fatty Acids / metabolism*
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Fatty Acids / pharmacology
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Gene Expression / drug effects
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Gene Expression / genetics
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Glucose / metabolism*
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Glucose Transporter Type 1 / genetics
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Glucose Transporter Type 2 / genetics
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Glycogen / biosynthesis
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Humans
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Insulin / pharmacology
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Muscle Cells / drug effects*
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Muscle Cells / metabolism
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Muscle Fibers, Skeletal / drug effects
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Muscle Fibers, Skeletal / metabolism
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Muscle, Skeletal / cytology
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Muscle, Skeletal / metabolism*
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Oleic Acid / metabolism
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Oleic Acid / pharmacology
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Oxidation-Reduction
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Phospholipids / metabolism
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Serum Albumin, Bovine / pharmacology
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Triglycerides / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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CD36 Antigens
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Diglycerides
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Fatty Acids
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Glucose Transporter Type 1
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Glucose Transporter Type 2
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Insulin
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Phospholipids
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RNA, Messenger
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SLC2A1 protein, human
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SLC2A2 protein, human
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Triglycerides
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Carbon Dioxide
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Serum Albumin, Bovine
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Oleic Acid
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Glycogen
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Eicosapentaenoic Acid
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Diacylglycerol O-Acyltransferase
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3-Phosphoinositide-Dependent Protein Kinases
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Protein Serine-Threonine Kinases
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Glucose