Thus, hyperinsulinemia in mice fed a HFD over a long period induces decreased expression of FoxO transcription factors, for example, FoxO3a and FoxO6, suggesting that disturbance of FoxO-mediated transcription downstream of the insulin signaling pathway might be involved in the pathogenesis of obesity-associated cognitive dysfunction. The gene discussed is FOXO6; the disease is obesity due to melanocortin 4 receptor deficiency.