Our results proved that the inhibition of abnormal mTOR activation by RAPA administration to HFD-induced obese gerbils significantly reduced obesity-induced severe increases in levels of oxidative stress indicators and proinflammatory cytokines and microglial activation during pre- and/or post-ischemic phases and attenuated CA1 pyramidal neuronal death induced by 2 min of TI, without affecting blood glucose levels, serum lipid concentrations, or leptin levels as expected. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.