Figure 2.

Mitochondrial dysfunction and insulin resistance. Impaired mitochondria oxidative capacity leads to a decrease in metabolic substrate catabolism resulting in increased intramyocellular fatty acids availability, which may be channelled towards lipotoxic lipid species biosynthesis (i.e., ceramide and diacylglycerol) both of which have been associated with insulin resistance. Increased nutrient supplies also induce an increase in mitochondrial reactive oxygen species (ROS) production, which can directly induce insulin resistance and elicit oxidative damage to mitochondrial DNA, protein and lipid promoting the removal of damaged mitochondria by mitophagy.