INS and obesity due to melanocortin 4 receptor deficiency: AMPK is a heterotrimer complex consisting of a catalytic subunit α (α1, α2) and two regulatory subunits β (β1, β2) and γ (γ1, γ2, γ3) and is activated by phosphorylation of the α subunit at Thr172.215 AMPK functions as a “fuel gauge” to monitor cellular energy status and is highly conserved across all eukaryotic species.215,216 Growing evidence suggests that brain AMPK plays a pivotal role in the development of obesity by regulating feeding, insulin sensitivity, BAT thermogenesis, and browning of WAT (Fig. 3).217