We previously published that mice deficient for whole-body Fgf21 (Fgf21–/–) are refractory to GCGR-mediated prevention of diet-induced obesity (14), and DIO mice deficient for liver Fgf21 (Fgf21Δliver) exhibit partial reductions in body weight (13) in response to GCGR agonism, suggesting that FGF21 contributes to the antiobesity effects of GCGR signaling. Here, GCGR is linked to obesity due to melanocortin 4 receptor deficiency.