INS and Insulin resistance: The treatment of mice with MC4R antagonists and the knockout of the Mc4r gene in the hypothalamus led to hyperphagia, obesity, insulin resistance and reduced energy expenditure, while the treatment of obese rodents with MC4R agonists and the restoration of the Mc4r gene expression in the paraventricular hypothalamus of the Mc4r-/- mice resulted in the normalization of their body and fat weight, the decrease in appetite and the improvement of the glucose and insulin sensitivity [9–11, 13–15].