Fat partitioning and insulin sensitivity: robbing Peter to pay Paul?

The evidence is now compelling that an excess supply of fatty acids, beyond that required for energy needs, is a cause of muscle insulin resistance. Intramyocellular triglyceride accumulation is a marker of excess fatty acid supply to muscle, and it is now two decades since an association was recognized between intramyocellular triglyceride accumulation and insulin resistance (1). Arguably, the major issues now (2,3) are to first pin down the causal mechanisms between fatty acid oversupply and insulin resistance (the prevailing view is that triglycerides themselves do not cause insulin resistance because they localize within discrete lipid droplets), second, define and develop appropriate therapeutic strategies, and third, clarify the place of dysregulated lipid metabolism against other, not necessarily mutually exclusive, putative causes of insulin resistance (4).