These observations are consistent with findings regarding mirtazapine-induced increase of energy expenditure, reduction of lipid levels, and alleviation of hepatosteatosis and glycemia, all caused by increased FGF-21 levels (Figure S4); in both murine and nonhuman primate models of DM and obesity, FGF-21 is a key factor regulating the amelioration of glucose and lipid parameters [37]. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.