Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes

Low dose of oleate (0.05 mM) was sufficient to improve palmitate complete oxidation to CO2 (+ 29%, P < 0.05) and to alter the cellular acylcarnitine profile. Insulin-induced Akt phosphorylation was 48% higher in that condition vs. palmitate alone (p < 0.01). Although DAG and ceramide contents were significantly decreased with 0.05 mM of oleate vs. palmitate alone (− 47 and − 28%, respectively, p < 0.01), 0.25 mM of oleate was required to decrease p38 MAPK and PKCθ phosphorylation, thus further improving the insulin signaling (+ 32%, p < 0.05). By contrast, increasing oleate concentration from 0.25 to 0.5 mM, thus increasing total amount of FA from 0.75 to 1 mM, deteriorated the insulin signaling pathway (− 30%, p < 0.01). This was observed despite low contents in DAG and ceramides, and enhanced palmitate incorporation into TAG (+ 27%, p < 0.05). This was associated with increased incomplete FA β-oxidation and impairment of acylcarnitine profile. In conclusion, these combined data place mitochondrial β-oxidation at the center of the regulation of muscle insulin sensitivity, besides p38 MAPK and PKCθ.