FGF21 Regulates Sweet and Alcohol Preference

Fibroblast growth factor 21 (FGF21) is a hormone induced by various metabolic stresses, including ketogenic and high-carbohydrate diets, that regulates energy homeostasis. In humans, SNPs in and around the FGF21 gene have been associated with macronutrient preference, including carbohydrate, fat, and protein intake. Here we show that FGF21 administration markedly reduces sweet and alcohol preference in mice and sweet preference in cynomolgus monkeys. In mice, these effects require the FGF21 co-receptor β-Klotho in the central nervous system and correlate with reductions in dopamine concentrations in the nucleus accumbens. Since analogs of FGF21 are currently undergoing clinical evaluation for the treatment of obesity and type 2 diabetes, our findings raise the possibility that FGF21 administration could affect nutrient preference and other reward behaviors in humans. [Display omitted] •FGF21 suppresses sweet and alcohol preference but not bitter taste•The effects of FGF21 on taste preference require its action in the CNS•FGF21 decreases dopamine levels in the nucleus accumbens•FGF21 regulation of sweet preference also occurs in primates FGF21 has well-established beneficial metabolic effects. Talukdar et al. now extend this repertoire and reveal that FGF21 also suppresses sweet and alcohol preference in mice, and sweet preference in monkeys, by acting on the CNS. These effects are associated with decreased dopamine, a key neurotransmitter used in reward pathways.