Metabolic flexibility and obesity in children and youth

The concept of metabolic flexibility describes the ability of skeletal muscle to switch between the oxidation of lipid as a fuel during fasting periods to the oxidation of carbohydrate during insulin stimulated period. Alterations in energy metabolism in adults with obesity, insulin resistance and/or type 2 diabetes induce a state of impaired metabolic flexibility, or metabolic inflexibility. Despite the increase in the prevalence of type 2 diabetes in obese children and youth, less is known about the factors involved in the development of metabolic inflexibility in the paediatric population. Metabolic flexibility is conditioned by nutrient partitioning in response to feeding, substrate mobilization and delivery to skeletal muscle during fasting or exercising condition, and skeletal muscle oxidative capacity. Our aim in this review was to identify among these factors those making obese children at risk of metabolic inflexibility. The development of ectopic rather than peripheral fat storage appears to be a factor strongly linked with a reduced metabolic flexibility. Tissue growth and maturation are determinants of impaired energy metabolism later in life but also as a promising way to reverse metabolic inflexibility given the plasticity of many tissues in youth. Finally, we have attempted to identify perspectives for future investigations of metabolic flexibility in obese children that will improve our understanding of the genesis of metabolic diseases associated with obesity.