INS and obesity due to melanocortin 4 receptor deficiency: Obesity has been considered as a state of chronic metabolic disorder (34), and obesity-related hemodynamic factors (e.g., increased circulating blood volume and cardiac output) and metabolic factors (e.g., insulin resistance, visceral fat deposition and secretion of adipokines) may contribute to a series of adaptations/alterations in cardiac structure and function (35).