Muscle mitochondria and insulin resistance: a human perspective.

Reduced mitochondrial capacity in skeletal muscle has been suggested to underlie the development of insulin resistance and type 2 diabetes mellitus (T2DM). However, data obtained from human subjects concerning this putative relation indicate that the mitochondrial defect observed in diabetic muscle might be secondary to the insulin-resistant state instead of being a causal factor. Nonetheless, diminished mitochondrial function, even secondary to insulin resistance, may accelerate lipid deposition in non-adipose tissues and aggravate insulin resistance. Indeed, improving mitochondrial capacity via exercise training and calorie restriction is associated with positive metabolic health effects. Here we review muscle mitochondrial dysfunction in humans and propose that targeting muscle mitochondria to improve muscle oxidative capacity should be considered as a strategy for improving metabolic health.