FGF21 and obesity due to melanocortin 4 receptor deficiency: In mice with diet induced obesity (DIO), FGF21 mRNA expression was 4-fold higher than that seen in lean animals (Fig 1A; Lean Fed 0.22 ± 0.04; DIO fed 1.0 ± 0.23; p = 0.02) and a 50% fall was observed with fasting.