Animal studies reported that male and female ESR1 gene knockout mice developed features of the metabolic syndrome (MetS) including obesity caused by impaired fatty acid oxidation, glucose intolerance, and impaired insulin sensitivity, thus revealed the critical role of ESR1 in metabolic homeostasis (Heine et al., 2000; Ribas et al., 2010). The gene discussed is ESR1; the disease is obesity due to melanocortin 4 receptor deficiency.