J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500300-JLR200 on November 21, 2005

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Journal of Lipid Research, Vol. 47, 366-374, February 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Eicosapentaenoic acid (20:5 n-3) increases fatty acid and glucose uptake in cultured human skeletal muscle cells

Vigdis Aas*, Merethe H. Rokling-Andersen{dagger}, Eili Tranheim Kase§, G. Hege Thoresen§ and Arild C. Rustan1,§

* Faculty of Health Sciences, Oslo University College, Oslo, Norway
{dagger} Institute for Nutrition Research, University of Oslo, Oslo, Norway
§ Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway

Published, JLR Papers in Press, November 21, 2005.

1 To whom correspondence should be addressed. e-mail: arild.rustan{at}farmasi.uio.no

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 ß-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.

Supplementary key words human skeletal myotubes • lipid metabolism • glucose metabolism

Abbreviations: ASM, acid-soluble metabolite; BSA, bovine serum albumin; EPA, eicosapentaenoic acid; ERK, extracellular signal-regulated kinase; FCS, fetal calf serum; {alpha}MEM, minimum essential medium {alpha}; OA, oleic acid; PKB, protein kinase B; PL, phospholipid; PPAR{gamma}, peroxisome proliferator-activated receptor {gamma}; TAG, triacylglycerol


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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.