OBJECTIVE: The gene that codes for a novel uncoupling protein, UCP2, has been linked to obesity in animal models. Markers encompassing the UCP2 locus have been linked to energy expenditure in humans. We studied the role of a common amino acid substitution, replacing an alanine (A) with a valine (V) at codon 55, of the coding region of the UCP2 gene for 24‐h energy expenditure and respiratory quotient (RQ) in healthy subjects

METHODS: 24‐h energy expenditure and RQ were measured in calorimeters in 60 healthy subjects. The UCP2 polymorphism was determined by restriction fragment length polymorphism-generating polymerase chain reaction.

RESULTS: Age, gender and body fat were not different between groups, the number of subjects in each groups was A/A: 35%(n= 21), A/V: 48%(n= 29), and V/V: 17%(n= 10). Twenty‐four‐hour energy expenditure, adjusted for fat-free mass, fat mass, and spontaneous physical activity, was 311 kJ/d lower (95% confidence interval: 24–598 kJ/d, P= 0.03) in the V/V homozygotes than in the A/A and A/V genotypes. The V/V had∼ 20% higher 24‐h spontaneous physical activity, particularly higher at night (P< 0.005). Energy expenditure due to higher spontaneous physical activity counteracted the V/V group’s lower 24‐h resting energy expenditure for a given body size and composition. 24‐h RQ adjusted for energy balance, age, sex and spontaneous physical activity, was higher in the V/V homozygotes than in the AA and A/V groups (P< 0.05).

CONCLUSIONS: Subjects with the V/V genotype of the UCP2 gene exhibit an enhanced metabolic efficiency and lower fat oxidation than the A/A and A/V genotypes.