INSR and Insulin resistance: Several previous studies demonstrated that chronic HFD consumption induced obese-insulin resistance prior to causing brain insulin resistance, as indicated by decreasing phosphorylation of insulin receptors (IR), insulin receptor substrate (IRS) and downstream signaling, including PI3K-Akt, GSK3β, and AMPK pathways (4, 6, 7, 9–14, 16–19, 28–31, 91–94).