A dominant appetite for protein drives increased energy intake in humans when the proportionof protein in the diet is reduced down to approximately 10% of total energy. Compensatoryfeeding for protein is apparent over a 12 d period but the mechanisms driving thisregulation are not fully understood. Fibroblast growth factor-21 (FGF-21) has been identifiedas a candidate protein signal as levels increase in the circulation when dietary protein islow. The aim of this randomised controlled trial was to assess whether changes in percentdietary protein over a 4 d ad libitum experimental period in lean, healthy participants influencedenergy intake, metabolic health, circulating FGF-21 and appetite regulating hormonesincluding ghrelin, glucagon like peptide-1 and cholecystokinin. Twenty-two lean,healthy participants were fed ad libitum diets containing 10, 15 and 25% protein, over three,4 d controlled, in-house experimental periods. Reduced dietary protein intake from 25% to10% over a period of 4 d was associated with 14% increased energy intake (p = 0.02) aspreviously reported, and a 6-fold increase in fasting circulating plasma FGF-21 levels(p