While endogenous FGF21 imposes no effects on metabolic rates and body weight during chow diet feeding24,25, its role for systemic metabolism is established under conditions of obesity, where administration of exogenous FGF21 (or FGF21 analogs) leads to improved metabolic profiles in mice and humans26,27. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.