Palmitic and Lauric Acid Differently Modulated Skeletal Muscle Mitochondrial Dynamics, Membrane Potential and Metabolic Inflammation in Human Primary Myotubes

The chain-length of saturated fatty acids (SFA) may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. Thus, the aim of this study was to compare the effect of palmitic (PA) and lauric (LA) acid on skeletal muscle mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500µM). After 24 h, the expression of interleukin-6 (IL-6) was assessed by qPCR, while Western blot was used to quantify the inhibitor of nuclear factor kappa-B (IkBα) and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, but not LA, triggered an inflammatory response marked by an upregulation of IL-6 mRNA (p < 0.01) and a decrease in IkBα (p < 0.05). Furthermore, while PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA-induced mitochondrial fragmentation (p < 0.001), decreased MFN-2 (p < 0.05) and caused a drop in mitochondrial membrane potential compared to control (p < 0.01), with these effects being absent in LA-treated cells. Thus, LA, contrarily to PA, did not trigger pathogenetic mechanisms linked with insulin resistance and therefore represents a potentially healthier SFA to preserve skeletal muscle .metabolic health