Figure 7. Proposed model by which insulin sensitizing through aerobic exercise and metformin correct impairments in brain mitochondrial function with insulin resistance.

Brain insulin resistance induced through high-fat diet (HFD) or intranasal insulin receptor antagonism increases ROS, which leads to oxidative damage to DNA and proteins and protein accumulation, due to inadequate clearance of damaged proteins. Collectively, these impairments in mitochondrial protein function leads to decreased ATP production. By restoring insulin sensitivity, aerobic exercise and metformin prevent and/or reverse these altered functions.