Greater decrease in 24-h energy expenditure (EE) during fasting and smaller increase in 24-h EE during low-protein overfeeding (“thrifty” metabolic phenotype) predict weight gain. As thyroid hormones (TH) are implicated in energy intake and metabolism, we assessed whether TH concentrations are altered by 24-h fasting or overfeeding diets with varying protein content and correlate with changes in EE.


Euthyroid, healthy subjects (n=58) underwent 24-h dietary interventions including fasting and five overfeeding diets (200% of energy requirements) in a crossover design within a whole-room calorimeter to measure 24-h EE. Overfeeding diets included three diets with 20%-protein, one with 3%-protein (low protein feeding, LPF), and one with 30%-protein (high protein feeding, HPF). Plasma free thyroxine (FT4), triiodothyronine (FT3), and fibroblast growth factor 21 (FGF21) concentrations were measured after overnight fast the morning of and after each diet.


On average, FT4 increased by 8% (+0.09 ng/dL, p<0.001) while FT3 decreased by 6% (−0.17 pg/mL, p=0.001) after 24-h fasting, whereas both decreased by 5% (−0.08, p<0.0001) and 4% (−0.14, p=0.008) following HPF, respectively. Greater decreases in FT3 after HPF were associated with larger decreases in FGF21 (r=0.40, p=0.005). Following LPF, mean FT3 increased by 6% (+0.14 pg/mL, p=0.003) with no change in FT4 (p=0.7). No associations were observed between TH concentrations and changes in 24-h EE during any diet (all p>0.07).


Acute changes in food intake induce small changes in TH concentrations only after diets with low or high protein content. The FT3-FGF21 association after high-protein overfeeding suggests a role for TH in inhibiting FGF21 secretion by the liver during protein excess. These results indicate that TH are involved in protein metabolism; however, they do not mediate the short-term EE response to diets that characterizes the metabolic phenotypes.