In hyperphagia and obesity, hyperactivation of both tyrosine phosphatases is observed in the hypothalamus, which leads to a decrease in the sensitivity of hypothalamic neurons to insulin, and in prolonged consumption of saturated fatty acids, JNK1 activity increases in the hypothalamus and other regions of the brain, which reduces the activity of IRS proteins and leads to central IR [124,125]. The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.