Triiodothyronine-mediated up-regulation of UCP2 and UCP3 mRNA expression in human skeletal muscle without coordinated induction of mitochondrial respiratory chain genes 1
- PIERRE BARBE*,2,
- DOMINIQUE LARROUY*,2,
- CATHERINE BOULANGER*,
- EMMANUEL CHEVILLOTTE†,
- NATHALIE VIGUERIE*,
- CLAIRE THALAMAS‡,
- MANEL OLIVA TRASTOY*,
- MARINA ROQUES†,
- HUBERT VIDAL† and
- DOMINIQUE LANGIN*,3
- *INSERM Unit 317, Institut Louis Bugnard, Université Paul Sabatier, Hôpital Rangueil, Toulouse, France;
- †INSERM Unit 449, Faculté de Médecine RTH Laennec, Lyon, France; and
- ‡Centre d’Investigation Clinique, Hôpital Purpan, Toulouse, France
- ↵Correspondence: 3Correspondence: INSERM U317, Institut Louis Bugnard, Bâtiment L3, CHU Rangueil, 31403 Toulouse Cedex 4, France. E-mail: langin{at}rangueil.inserm.fr
SPECIFIC AIMS
Triiodothyronine (T3) increases mitochondrial respiration and promotes, in rodents, the uncoupling between oxygen consumption and ATP synthesis. The T3 effect is mediated partly through transcriptional control of genes encoding mitochondrial proteins. Here, 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.
PRINCIPAL FINDINGS
1. In vivo treatment with T3 increases UCP2 and UCP3 mRNA levels in human skeletal muscle without induction of respiratory chain gene expression
Ten young healthy men were treated for 14 days with 75 μg per day of T3. The treatment induced a 1.7-fold increase in free T3 levels (P < 0.005). Resting metabolic rate adjusted for lean body mass was increased by 15% (P < 0.05). The respiratory quotient was decreased (P < 0.05) and plasma NEFA levels were not significantly modified by the treatment.
T3 treatment induced a 1.7- and 2.4-fold increase in UCP2 and total UCP3 mRNA levels (P < 0.01), respectively (Fig. 1⇓ ). The mRNA levels of proteins of the respiratory chain and factors controlling their expression were also determined. There was no change in nucleus-encoded cytochrome c oxidase subunit 4 (COX4), nuclear respiratory factor 1 (NRF1), and PPARγ coactivator 1 (PGC1) mRNA expression. Before and during the T3 treatment, NRF1 and PGC1 mRNA levels were positively correlated (r=0.62, P<0.05 and r=0.76, P<0.02, respectively). Mitochondrial transcription factor A (mtTFA) and mitochondrion-encoded COX2 mRNA expression were not modified by the treatment.
Individual variations in skeletal muscle UCP2 and UCP3 mRNA levels of 10 healthy men treated with T3 for 14 days.
2. T3 induces UCP2 and UCP3 mRNA expression in primary culture of human skeletal muscle cell
The effect of T3 was studied in human muscle cells differentiated into myotubes. After 24 h of incubation, T3 induced a dose-dependent increase in UCP2 mRNA levels with a 4.5-fold induction at 100 nM. In untreated myotubes, UCP3 mRNA levels were much lower than in skeletal muscle …
