Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes.
Triiodothyronine (T3) increases mitochondrial respiration and promotes the uncoupling between oxygen consumption and ATP synthesis. T3 effect is mediated partly through transcriptional control of genes encoding mitochondrial proteins. We determined the effect of T3 on mRNA levels of uncoupling proteins (UCP) and proteins involved in the biogenesis of the respiratory chain in human skeletal muscle and on UCP2 mRNA expression in adipose tissue. Ten young, healthy males received 75 to 100 5g of T3 per day for 14 days. The increase in plasma-free T3 levels was associated with an increase of resting metabolic rate and a decrease of respiratory quotient. In skeletal muscle, treatment with T3 induced a twofold increase of both UCP2 and UCP3 mRNA levels (p c oxidase subunits 2 and 4, nuclear respiratory factor 1, mitochondrial transcription factor A, and the co-activator PGC1 did not change during the treatment. In adipose tissue, UCP2 mRNA levels increased threefold. The direct effect of T3 on skeletal muscle an d adipose tissue UCP2 and UCP3 mRNA expression was demonstrated in vitro in human primary cultures. Our data show that T3 induces UCP2 and UCP3 mRNA expression in humans. In skeletal muscle, UCP regulation by T3 is not associated with the transcriptional regulation of respiratory chain proteins.
Barbe
P
P
INSERM Unit 317, Institut Louis Bugnard, Université Paul Sabatier, Hôpital Rangueil, Toulouse, France.
Larrouy
D
D
Boulanger
C
C
Chevillotte
E
E
Viguerie
N
N
Thalamas
C
C
Oliva Trastoy
M
M
Roques
M
M
Vidal
H
H
Langin
D
D
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D008954:Models, Biological; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D015854:Up-Regulation / Q000187:drug effects*
D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial 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; D014284:Triiodothyronine