INS and Insulin resistance: Regarding obese-insulin resistant models, energy restriction attenuated metabolic disturbance and preserved dendritic spine density (31), while the vagus nerve stimulation led to attenuated peripheral insulin resistance as well as improved brain function, as indicated by improved brain insulin sensitivity/brain mitochondrial function/cognitive function, and reduced brain inflammation, /brain oxidative stress/ brain apoptosis/dendritic spine loss (13).