INSR and obesity due to melanocortin 4 receptor deficiency: Senescent ECs induced by Ras cause systemic metabolic dysfunction, obesity, and diabetes mellitus by inhibiting the insulin/insulin receptor/insulin receptor substrate/phosphoinositide 3-kinase (PI3K)/Akt signaling and enhancing the insulin receptor/son of sevenless/growth factor receptor bound protein/mitogen-activated protein kinase (MAPK) signaling (Figure 3) (King et al., 2016).