Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects

Aims/hypothesis. The regulation of uncoupling protein 2 and uncoupling prot ein 3 gene expression in skeletal muscle has recently been the focus of int ense interest. Our aim was to determine expression of uncoupling protein 2 and 3 in skeletal muscle from tetraplegic subjects, a condition representin g profound muscle inactivity. Thereafter we determined whether exercise tra ining would modify expression of these genes in skeletal muscle. Methods. mRNA expression of uncoupling protein 2 and 3 was determined using quantitative reverse transcription-polymerase chain-reaction. Results. Expression of uncoupling protein 2 and 3 mRNA was increased in ske letal muscle from tetraplegic compared with able-bodied subjects (3.7-fold p < 0.01 and 4.1-fold, p < 0.05, respectively). A subgroup of four tetraple gic subjects underwent an 8-week exercise programme consisting of electrica lly-stimulated leg cycling (ESLC, 7 ESLC sessions/week). This training prot ocol leads to increases in whole body insulin-stimulated glucose uptake and expression of genes involved in glucose metabolism in skeletal muscle from tetraplegic subjects. After ESLC training, uncoupling protein 2 expression was reduced by 62% and was similar to that in able-bodied people. Similarl y, ESLC training was associated with a reduction of uncoupling protein 3 ex pression in skeletal muscle from three of four tetraplegic subjects, howeve r, post-exercise levels remained increased compared with able-bodied subjec ts. Conclusion/interpretation. Tetraplegia is associated with increased mRNA ex pression of uncoupling protein 2 and 3 in skeletal muscle. Exercise trainin g leads to normalisation of uncoupling protein 2 expression in tetraplegic subjects. Muscle disuse and physical activity appear to be powerful regulat ors of uncoupling protein 2 and 3 expression in human skeletal muscle.