MESSENGER-RNA EXPRESSION OF THE LONG AND SHORT FORMS OF UNCOUPLING PROTEIN-3 IN OBESE AND LEAN HUMANS

Uncoupling protein-3 (UCP3) is a mitochondrial protein expressed in sk eletal muscle, an important site of thermogenesis in humans. By uncoup ling respiration from ATP synthesis, UCP3 might be involved in the con trol of energy expenditure. Two transcripts encoding long (UCP3(L)) an d short (UCP3(S)) form are generated from the human UCP3 gene. UCP3(S) is predicted to encode a protein which lacks the C-terminus of UCP3(L ), a region which contains motifs critical for uncoupling activity. We have investigated the regulation of UCP3(L) and UCP3(S) mRNAs in lean and obese humans. A specific reverse transcription-competitive polyme rase chain reaction assay was developed to separately quantify the two mRNAs. Each transcript represents half of total UCP3 mRNA in 16 vastu s lateralis muscle samples. The amounts of UCP3(L) and UCP3(S) mRNAs d id not differ between obese and lean subjects. The effect of fasting w as studied in six lean and seven obese subjects maintained on a hypoca loric diet (1045 kJ/d) for 5 days. Calorie restriction results in an a pproximately threefold increase of UCP3(L) and UCP3(S) mRNA levels. Th e induction was similar in lean and obese subjects. The data suggest t hat there is no major alteration of UCP3 gene expression and regulatio n at the level of transcription and alternative splicing in skeletal m uscle of obese subjects.