FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

Abstract

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. When the number of responses required to access protein reward varied, protein-restricted mice exhibited higher operant responses at moderate to high response requirements. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (Klb