PPARGC1A and obesity due to melanocortin 4 receptor deficiency: In the brain of monkeys with long standing diet-dependent obesity, it was shown that AKT and other insulin signaling factors are maximally increased, resulting in hyperphosphorylation of mTOR, FOXO1, FOXO3a, FOXO4 and subsequent decrease in PGC1α expression that, together, maintain neuronal integrity.