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

Abstract

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 [ 14 C]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 [ 14 C]oleate into all lipid classes for EPA-treated myotubes. Fatty acid b-oxidation was unchanged, and complete oxidation (CO 2 ) decreased in EPA-treated cells. Basal glucose transport and oxidation (CO 2 ) 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.-Aas, V

Fatty Acid Incubation of Myotubes From Humans With Type 2 Diabetes Leads to Enhanced Release of β-Oxidation Products Because of Impaired Fatty Acid Oxidation

“…7C and D). Preincubation of myotubes with the naturally occurring fatty acids enhanced 14 C-palmitic acid uptake in line with previous observations (8,10), and EPA was more effective than oleic acid (Fig. 7C and D).…”

“…Moreover, EPA markedly increased the level of C16:1-CoA, which has recently been shown to function as a lipokine improving peripheral insulin action (44) and glucose metabolism in L6 rat myotubes (45). In addition, incubation of myotubes from normal lean subjects with EPA improved glucose uptake, despite an increased incorporation of 14 C-oleic acid into TAG (10). In rats, EPA also improved insulin resistance while increasing imTAG levels (46).…”

“…Very long-chain -3 fatty acids, including eicosapentaenoic acid (EPA), may protect against skeletal muscle insulin resistance caused by high-fat feeding in vivo (1,13). PUFAs may also promote increased TAG accumulation without impairing insulin-stimulated glucose uptake in myotubes (10,11). The sulfur-substituted fatty acid analog tetradecylthioacetic acid (TTA) is a pan-peroxisome proliferator-activated receptor (pan-PPAR) activator that reduces plasma lipids and enhances hepatic fatty acid oxidation in rodents (14).…”

Metabolic switching of human myotubes is improved by n-3 fatty acids

“…In the present study we did not observe increased glucose oxidation after pretreatment with EPA compared with control, in contrast to previous reports ( 23,24 ). This fi nding might be due to different experimental conditions, such as incubation time and concentration of fatty acids used.…”

“…By contrast, incubation of myotubes with the unsaturated fatty acid oleic acid (OA) increased triacylglycerol (TAG) accumulation without inhibiting insulin action ( 21,22 ). Pretreatment of human myotubes with EPA has been shown to promote increased uptake of fatty acids and increased TAG accumulation, also compared with pretreatment with OA, without impairing insulin-stimulated glucose uptake ( 23,24 ). Wensaas et al also showed that the level of total acyl-CoA was reduced after EPA pretreatment versus OA ( 24 ).…”