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Abstract
The regulation of the selection of appropriate fuels by skeletal muscle is important both in terms of muscle energy metabolism and also in the regulation of whole-body fuel supply and utilization. Complex interplay between carbohydrate and lipid fuels was identified over 40 years ago. More recently, there has been a rapid expansion in our knowledge of mechanisms regulating muscle fuel handling and the potential consequences of fuel dysregulation for health and disease. Fatty acids, and their derivatives, can directly influence muscle insulin signaling and, therefore, underlie the etiology of insulin resistance. In addition, the role of lipid-regulated nuclear hormone receptors, including the peroxisome proliferator-activated receptors, has rapidly advanced. Finally, the role of adipokines, derived from adipose tissue, in the modulation of muscle lipid handling and insulin action has emphasized the existence of an adipomuscular axis that can underlie metabolic changes in disease states, including obesity and inflammation.