THRB and obesity due to melanocortin 4 receptor deficiency: In summary, we have shown that hypothalamic TRβ is an important physiological regulator of energy homeostasis because TRβ knockdown in the VMH results in a phenotype of hyperphagia and severe obesity that is comparable to some of the most extreme forms of monogenic obesity (Tecott et al., 1995, Yaswen et al., 1999).