Free fatty acid effects on myokine production in combination with exercise mimetics

Scope: We aimed to study the effects of free fatty acids (FFAs) alone and combined with the exercise mimetics adrenaline and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in the production of IL6, IL15 and Irisin in muscle cells, using a time-sequential model. Methods and results: Differentiated C2C12 myotubes were treated with FFA, adrenaline or AICAR alone for 0, 1, 3, 8, 12 and 24 h and with double or triple combinations for 0, 3 and 24 h. Levels of mRNA in cells and protein in the medium were measured. Adrenaline, AICAR and FFA showed no significant effects on Irisin expression, while the presence in the culture of adrenaline and/or AICAR decreased IL15 mRNA expression. On contrary, the three signals showed a deep, rapid impact on the IL6 induction, especially when both AICAR and FFA were present. Conclusion: The different response in IL6 versus IL15 regulation may be explained by their different energy-activating versus muscle-cell-hypertrophy suggested roles, considering that adrenaline and AMPK are involved in the activation of energy-generating pathways. Moreover, the results suggest FFAs are components thatmay regulate IL6 production and may have a role in muscle-adipose tissue crosstalk.