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

Vigdis Aas, Merethe Helene Rokling-Andersen, Eili Tranheim Kase, G. Hege Thoresen, and Arild Christian Rustan

Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Blindern, Oslo 0316

Corresponding Author: arild.rustan{at}farmasi.uio.no

The present 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 more than 2-fold increased after pre-incubation of myotubes with 0.6 mM EPA for 24 h, and incorporation into various lipid classes showed that cellular triacylgycerol (TAG) and phospholipids (PL) were 2-3-fold elevated compared to control cells. After exposure to oleic acid (OA) TAG was 2-fold increased. Insulin (100 nM) further increased 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 2-fold elevated 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 mRNA expression was increased after EPA and OA treatment compared to control cells. Moreover, GLUT1 expression was 2.5-fold increased by EPA, whereas GLUT4 expression was unchanged, and activites of mitogen the activated protein kinases p38 and ERK was decreased after treatment with OA compared to EPA. Taken 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.

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