Changes in the Skeletal Muscle Proteome in Response to Saturated and Mono-unsaturated Fatty Acids

The prevalence of Type 2 Diabetes Mellitus (T2DM) in recent years and its association with many biomarkers of ill- health such as Obesity has thrust this condition into the research ‘spotlight’. Elevated levels of plasma fatty acids, especially saturated fatty acids in the obese are correlated to insulin resistance and as such much focus at both the basic and complex level has tried to elucidate the role of saturated fatty acids on insulin signaling in metabolic tissues such as the liver and skeletal muscle. Skeletal muscle is particularly important in the context of T2DM as it is the largest ‘glucose sink’ with more than 90% of glucose being up taken in response to insulin. Previous studies have shown that the saturated fatty acid Palmitate induces insulin resistance in skeletal muscle cells, whereas the unsaturated fatty acid Palmitoleate enhances insulin sensitivity in skeletal muscle. The aim of this study was to confirm or refute the previously reported effects of Palmitate and Palmitoleate on glucose uptake and PKB phosphorylation in C2C12 cells and carry out a thorough global proteomic screen to identify any changes across the proteome that may shed light on any effects noted. Our results show that a 16-hour treatment with 750 µM Palmitate increased intracellular Palmitate content 81%. Further, we observed that this increase in Palmitate caused a significant decrease in insulin-stimulated glucose uptake (p