The impact of the n-3 fatty acid eicosapentaenoic acid (EPA) on metabolic switching in human skeletal muscle cells

Our recent studies with differentiated human skeletal muscle cells (myotubes) suggests a positive role for the n-3 fatty acid eicosapentaenoic acid (EPA) compared to the other monounsaturated and saturated fatty acids (FAs) in improving overall metabolic switching in skeletal muscle in vitro. This might contribute to the beneficial health effects of dietary intake of very long-chain n-3 fatty acids. In a study using myotubes established from lean healthy donors we showed that incubation of EPA for one day increased suppressibility, the ability of acute glucose to suppress FA oxidation. Substrate-regulated flexibility, the ability to increase FA oxidation when changing from a high glucose, low fatty acid condition (“fed”) to a high fatty acid, low glucose (“fasted”) condition, was also increased by EPA. Adaptability, the capacity to increase FA oxidation with increasing FA availability, was enhanced after pretreatment with several FAs (EPA, linoleic acid (LA) and palmitic acid (PA)). EPA present in the cell after one day was significantly less than the other FAs, probably due to a higher oxidation rate. Yet, EPA, LA and oleic acid (OA) treatment increased the number of lipid droplets (LDs) in myotubes. LD volume and intensity, as well as mitochondrial mass were independent of FA pretreatment. Microarray and PCR analysis showed that EPA regulated more genes than the other FAs, and that specific pathways involved in carbohydrate metabolism were induced only by EPA. The present study suggests a favorable effect of EPA on skeletal muscle metabolic switching. Additional experiments with ALA (α-linolenic acid) and DHA (docosahexaenoic acid) indicated that the metabolic effects could be due to a general quality of n-3 FAs. Based on findings from this study we also suggest the use of three parameters called suppressibility, adaptability and substrate-regulated flexibility in functional studies of fuel selection and energy metabolism in cell cultures. References: Hessvik NP, Bakke SS et al, “Metabolic switching of human myotubes is improved by n-3 fatty acids.”, J Lipid Res. 2010 Aug;51(8):2090-104.