The causal link between obesity and IR lies in the elevated levels of proinflammatory adipokines, such as IL-6 and TNF-α, released by adipose tissue following fat accumulation, which worsens tissue responses to insulin, thus resulting in T2D, dyslipidemia and hypertension [29, 35, 91–94]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.