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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, Eili Tranheim Kase, G. Hege Thoresen and Arild C. Rustan^1,

^* Faculty of Health Sciences, Oslo University College, Oslo, Norway
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; MEM, minimum essential medium ; OA, oleic acid; PKB, protein kinase B; PL, phospholipid; PPAR, peroxisome proliferator-activated receptor ; TAG, triacylglycerol

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