Fat Feeding and Muscle Fat Deposition Eliciting Insulin Resistance
Skeletal muscle insulin resistance, generally deﬁned as a reduced ability of insulin to stimulate tissue utilization and storage of glucose, is an early and major perturbation in the conditions now characterized as “syndrome X” or “insulin resistance syndrome”. These states which include obesity, type 2 diabetes mellitus, dyslipidemia and hypertension, are known to be inﬂuenced by dietary factors, and are reaching epidemic proportions in many societies with a high caloriﬁc intake. In this review we consider the growing body of evidence which links insulin resistance with an increase in fatty acid availability in muscle and liver, the major target tissues for insulin action where insulin resistance occurs. We also consider possible causal links whereby increased muscle lipid accumulation can result in impaired insulin signaling and insulin resistance, and therapeutic options for ameliorating insulin resistance based on a “lipid-lowering” approach.