An animal model study demonstrated that ESR1 knockout mice exhibited insulin resistance, glucose tolerance impairment and obesity [87]; moreover, Zhai et al. demonstrated the cardioprotective role of estrogen receptor-α, an estrogen receptor encoded by ESR1, by investigating ischemia-reperfusion injury in male estrogen receptor-α knockout mice; they reported more severe myocardial damage and higher incidence of ventricular arrythmias in knockout mice hearts compared to control hearts [88]. Here, ESR1 is linked to obesity due to melanocortin 4 receptor deficiency.