Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects.
OBJECTIVE
The regulation of uncoupling protein 2 and uncoupling protein 3 gene expression in skeletal muscle has recently been the focus of intense interest. Our aim was to determine expression of uncoupling protein 2 and 3 in skeletal muscle from tetraplegic subjects, a condition representing profound muscle inactivity. Thereafter we determined whether exercise training 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 skeletal 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 tetraplegic subjects underwent an 8-week exercise programme consisting of electrically-stimulated leg cycling (ESLC, 7 ESLC sessions/week). This training protocol 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. Similarly, ESLC training was associated with a reduction of uncoupling protein 3 expression in skeletal muscle from three of four tetraplegic subjects, however, post-exercise levels remained increased compared with able-bodied subjects.


CONCLUSIONS
Tetraplegia is associated with increased mRNA expression of uncoupling protein 2 and 3 in skeletal muscle. Exercise training leads to normalisation of uncoupling protein 2 expression in tetraplegic subjects. Muscle disuse and physical activity appear to be powerful regulators of uncoupling protein 2 and 3 expression in human skeletal muscle.
Hjeltnes
N
N
Sunnaas Hospital, Nesoddtangen, Norway.
Fernström
M
M
Zierath
J R
JR
Krook
A
A
D000328:Adult; D015992:Body Mass Index; D002352:Carrier Proteins / Q000378:metabolism*; D015444:Exercise; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008931:Mitochondria, Muscle; D024101:Mitochondrial Proteins; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal; D010085:Oxidative Phosphorylation; D011506:Proteins / Q000378:metabolism*; D011782:Quadriplegia / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014475:Uncoupling Agents / Q000378:metabolism*; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3