γ-Linolenic acid increases expression of key regulators of lipid metabolism in human skeletal muscle cells.

Abstract

Control of skeletal muscle fat metabolism is regulated acutely through Peroxisome Proliferator Activated Receptor (PPAR) {delta} activation and its downstream intracellular targets. The purpose of this study was to determine whether fatty acids with high binding affinity for PPAR{delta} can elevate the expression of genes related to fatty acid oxidation and indicators of mitochondrial biogenesis in cultured human skeletal myotubes. Myotubes were treated for 72 hours with one of four conditions: (i) Control (CON); (ii) Eicosapentaenoic acid (EPA 250M); (iii) {gamma}-linolenic acid ({gamma}-LA 250M); (iv) PPAR{delta} Agonist (GW501516 10nM). Incubation with {gamma}-LA induced increases in the gene expression of CD36 (p= 0.005), HADHA (p= 0.022) and PDK4 (p=0.025) in comparison with CON, with no further differences observed between conditions. Furthermore, intensity of MitoTracker(R) Red immunostaining in myotubes increased following incubation with {gamma}-LA (p[≤] 0.001) and EPA (p= 0.005) however these trends were not mirrored in the expression of PGC-1 as might be expected. Overall, {gamma}-LA elevates levels the transcription of key intracellular regulators of lipid metabolism and transport in human myotubes, which may be clinically beneficial in the control of metabolic diseases.