It is possible that in SFDIOmales, the FGF21-induced improvement in glucose tolerancewas associated with a decrease in plasma concentration ofleptin and fatty acids which are key risk factors for insulinresistance at obesity (Yang et al., 2018; Zhang Q. et al., 2019).Zhao and coauthors, using genetic approaches and a leptinneutralizing antibody, demonstrated that in obese mice, apartial reduction of plasma leptin levels restores hypothalamicleptin sensitivity and effectively enhances glucose toleranceand insulin sensitivity (Zhao et al., 2019). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.