Skeletal Muscle Triglyceride - An aspect of regional adiposity and insulinresistance

Recent evidence derived from four independent methods indicates that an exc ess triglyceride storage within skeletal muscle is linked to insulin resist ance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid o xidation during postabsorptive conditions are prominent, leading to diminis hed use of fatty acids and increased esterification and storage of lipid wi thin skeletal muscle. These impairments in fatty acid metabolism during fas ting conditions may be related to a metabolic inflexibility in insulin resi stance that is not limited to defects in glucose metabolism during insulin- stimulated conditions. Thus, there is substantial evidence implicating pert urbations in fatty acid metabolism during accumulation of skeletal muscle t riglyceride and in the pathogenesis of insulin resistance. Weight loss by c aloric restriction improves insulin sensitivity, but the effects on fatty a cid metabolism are less conspicuous. Nevertheless, weight loss decreases th e content triglyceride within skeletal muscle, perhaps contributing to the improvement in insulin action with weight loss. Alterations in skeletal mus cle substrate metabolism provide insight into the link between skeletal mus cle triglyceride accumulation and insulin resistance, and they may lead to mote appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.