The adipokines, including adiponectin and leptin, have been demonstrated to signal through the hypothalamus to control whole-body metabolism, including modulation of sympathetic output to adipose tissue (Wang and He 2018) and directly modulate macrophage status in WAT, and thermogenesis in BAT during obesity (Cereijo et al. 2018; Larabee et al. 2020). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.