ABSTRACT
Obesity affects whole-body energy metabolism through alterations in skeletal muscle metabolic flux. For example, flux through protein synthesis and breakdown pathways is decreased despite no changes in muscle mass and an increase in plasma amino acids. Shifts in carbohydrate metabolism result in depressed insulin signaling transduction that leads to insulin resistance and an increased risk of type 2 diabetes. These alterations are compounded with decreased and inefficient lipid oxidation. These deficits seem to share a common nexus, which is a reduction in the mitochondrial capacity to oxidize substrate. For example, skeletal muscle mitochondrial networks appear more unorganized and dysregulated, and the chronic production of reactive oxygen species results in a shift toward an oxidative redox environment within the cell. These changes in skeletal muscle metabolism promote positive lipid balance, metabolic inflexibility, and weight gain.
