It also shows that IL-6 mediates in small part the links between obesity, insulin resistance and cardio-metabolic diseases, which has been a prevalent hypothesis in the field due to the evidence that the adipose tissue of insulin-resistant obese people is infiltrated with inflammatory cells [5,63] and displays an enhanced secretion of IL-6, tumor necrosis factor alpha and other pro-inflammatory mediators [13,61,62]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.