After first observing that Mfn2 expression was significantly and consistently decreased in the hypothalamus of mice in response to HF feeding from 4 days up to as long as 12 weeks, Schneeberger and colleagues [29] demonstrated that Mfn2 deletion selectively in POMC neurons caused severe obesity that was accompanied by impaired post-translational POMC cleavage into α-MSH. This evidence concerns the gene POMC and obesity due to melanocortin 4 receptor deficiency.