Impact of physical activity on brain oxidative metabolism and intrinsic capacities in young swiss mice fed a high fat diet.

Type 2 diabetes and obesity characterized by hallmarks of insulin resistance along with an imbalance in brain oxidative metabolism would impair intrinsic capacities (ICs), a new concept for assessing mental and physical functioning. Here, we explored the impact of physical activity on antioxidant responses and oxidative metabolism in discrete brain areas of HFD or standard diet (STD) fed mice but also its consequences on specific domains of ICs. 6-week-old Swiss male mice were exposed to a STD or a HFD for 16 weeks and half of the mice in each group had access to an activity wheel and the other half did not. As expected HFD mice displayed peripheral insulin resistance but also a persistent inhibition of aconitase activity in cortices revealing an increase in mitochondrial reactive oxygen species (ROS) production. Animals with access to the running wheel displayed an improvement of insulin sensitivity regardless of the diet factor whereas ROS production remained impaired. Moreover, although the access of the running wheel did not influence mitochondrial biomass, in the oxidative metabolism area, it produced a slight decrease in brain SOD1 and catalase expression notably in HFD fed mice. At the behavioural level, physical exercise produced anxiolytic/antidepressant-like responses and improved motor coordination in both STD and HFD fed mice. However, this non-pharmacological intervention failed to enhance cognitive performance. These findings paint a contrasting landscape about physical exercise as a non-pharmacological intervention for positively orienting the aging trajectory.