Vinales KL, et al. - Given that the change in energy expenditure (EE) following a low-protein overfeeding diet is a predictor of weight change in humans and a feature of the “thrifty” metabolic phenotype, researchers examined the relationship between circulating fibroblast growth factor 21 (FGF21) and EE in humans. For this investigation, they evaluated the post–24-hour changes in plasma FGF21 concentrations of seven dietary interventions with different macronutrient content while in a whole-room indirect calorimeter in 64 healthy volunteers with normal glucose regulation. Researchers noted that individuals with smaller increases in FGF21 following the low-protein/high-fat diet gained more weight after 6 months in free-living conditions. Results of this study suggested that people with a blunted FGF21 response to a low-protein diet have a thrifty metabolism and are at risk for future weight gain.