Fat Feeding And Muscle Fat Deposition Eliciting Insulin Resistance An Update

Skeletal muscle insulin resistance, defined as a reduced ability of insulin to stimulate tissue utilization and storage of glucose, is an early and major perturbation in the metabolic syndrome. Clinical conditions under the umbrella of the metabolic syndrome include obesity, type 2 diabetes, dyslipidemia, and hypertension, and are known to be influenced by lifestyle factors such as diet and activity. The metabolic syndrome is reaching alarming proportions in many societies. This chapter considers the increasingly compelling evidence that links insulin resistance with the situation when fatty acid supply exceeds energy demand in muscle, resulting in an accumulation of lipid in this tissue. This chapter is an update of a similar-titled chapter written some five years ago (1), and we highlight how knowledge has progressed since 2000. Considered are evidence for the association between fatty acid metabolism and muscle insulin resistance, possible causal links whereby increased muscle lipid accumulation could result in impaired insulin signalling and insulin resistance, and therapeutic options for ameliorating insulin resistance based on a “lipid-lowering” approach. We also consider how a scenario of excess fatty acid supply to muscle stands in relation to other emerging theories of factors contributing to muscle insulin resistance in obesity and similar states.