Because insulin, leptin, and possibly ghrelin function as key signals to the central nervous system in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose [88]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.