INCREASED UNCOUPLING PROTEIN-2 AND PROTEIN-3 MESSENGER-RNA EXPRESSIONDURING FASTING IN OBESE AND LEAN HUMANS

Uncoupling protein-2 and -3 (UCP2 and UCP3) are mitochondrial proteins that show high sequence homology with the brown adipocyte-specific UC P1. UCP1 induces heat production by uncoupling respiration from ATP sy nthesis. UCP2 is widely expressed in human tissues, whereas UCP3 expre ssion seems restricted to skeletal muscle, an important site of thermo genesis in humans, We have investigated the regulation of UCP2 and UCP 3 gene expression in skeletal muscle and adipose tissue from lean and obese humans, UCP2 and -3 mRNA levels were not correlated with body ma ss index (BMI) in skeletal muscle, but a positive correlation (r = 0.5 5, P < 0.01, n = 22) was found between UCP2 mRNA level in adipose tiss ue and BMI. The effect of fasting was investigated in eight lean and s ix obese subjects maintained on a hypocaloric diet (1,045 kJ/d) for 5 d. Calorie restriction induced a similar 2-2.5-fold increase in UCP2 a nd -3 mRNA levels in lean and obese subjects. To study the effect of i nsulin on UCP gene expression, six lean and five obese subjects underw ent a 3-h euglycemic hyperinsulinemic clamp. Insulin infusion did not modify UCP2 and -3 mRNA levels. In conclusion, the similar induction o f gene expression observed during fasting in lean and obese subjects s hows that there is no major alteration of UCP2 and -3 gene regulation in adipose tissue and skeletal muscle of obese subjects. The increase in UCP2 and -3 mRNA levels suggests a role for these proteins in the m etabolic adaptation to fasting.