Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans

Objectives: The molecular determinants of energy expenditure are presently unknown. Recently, two uncoupling protein homologues, UCP2 and UCP3, have b een identified. UCP2 is expressed widely, and UCP3 is expressed abundantly in skeletal muscle. Both could be important regulators of energy balance. I n this paper, we investigated whether altered UCP2 and UCP3 mRNA levels are associated with obesity or weight reduction. Research Methods and Procedures: UCP2, UCP3 long and short mRNA levels were examined in skeletal muscle and in white adipose tissue of lean, obese, an d weight-reduced individuals by RNase protection assay. Results: Expression of UCP2, UCP3S, and UCP3L mRNA in skeletal muscle was s imilar in lean individuals and in individuals with obesity at stable weight . In contrast, UCP3L and UCP3S mRNAs were decreased by 38% (p < 0.0059) and 48% (p < 0.0047), respectively, in 20% weight-reduced patients with obesit y at stable weight. In contrast, UCP2 mRNA levels were increased by 30% in skeletal muscle of 20% weight-reduced subjects with obesity. In a different set of patients, mostly lean, UCP3L mRNA in skeletal muscle was decreased by 28% (p = 0.0425) after 10% weight reduction at stable weight. Expression of UCP2 mRNA in subcutaneous adipose tissue was similar in lean individual s and in individuals with obesity, and was increased by 58% during active w eight loss. Discussion: Stabilization at reduced body weight in humans is associated wi th a decrease in UCP3 mRNA in muscle. It is possible that reduced UCP3 expr ession could contribute to decreased energy expenditure in weight-stable, w eight-reduced individuals.