Metabolic Response to Fasting Predicts Weight Gain During Low-Protein Overfeeding: Further Evidence for Spendthrift and Thrifty Metabolic Phenotypes

Abstract

Greater increase in 24-h energy expenditure (24EE) during overfeeding and smaller decrease in 24EE during fasting (“spendthrift” metabolic phenotype) are associated with more weight loss during sustained caloric restriction in obese subjects. It is unknown whether these metabolic characteristics can also defend weight gain during sustained overfeeding. We conducted the first proof-of-concept study in lean individuals to show that, after 6 weeks of 150% low-protein overfeeding, metabolically spendthrift subjects gained less weight, less fat mass and stored less calories. Those individuals who gained less weight had a greater relative 24EE increase following overfeeding. Fibroblast-growth-factor 21, a marker for metabolic spendthriftness, increased dramatically during low-protein overfeeding. These results confirm the existence of thrifty and spendthrift metabolic phenotypes and demonstrate that another mechanism by which spendthrift individuals may be less susceptible to weight gain is the ability to increase EE above that predicted for achieved body size, a process called “metabolic adaptation”.