Up-regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator-activated receptor ligands and 9-cis retinoic acid in L6 myotubes

Uncoupling protein 3 (UCP3), expressed abundantly in the skeletal muscle, i s one of the carrier proteins dissipating the transmitochondrial electroche mical gradient as heat, and thereby has been implicated in the regulation o f energy metabolism. We have investigated UCP3 mRNA expression in the widel y used L6 myocyte cell line by Northern blot analysis. UCP3 mRNA was not de tected in L6 myoblasts, but appeared after their differentiation to myotube s, The UCP3 mRNA level was increased when L6 myotubes were treated with inc reasing concentrations of triiodothyronine (T3), oleic acid, alpha-bromopal mitate and carbacyclin, a non-selective ligand of peroxisome proliferator-a ctivated receptors (PPARs), whereas it was not influenced when treated with selective ligands of PPAR alpha (WY 14 643) and PPAR gamma (troglitazone), A ligand of retinoid X receptor (RXR), 9-cis retinoic acid, was also effec tive by itself and in combination with carbacyclin in stimulating UCP3 mRNA expression, The mRNA analysis of individual PPAR isoforms revealed that L6 cell expressed a significant level of PPAR delta but undetectable levels o f PPAR alpha and PPAR gamma. These results suggest that UCP3 expression in myocytes is differentiation-dependent and regulated by the T3 receptor, RXR and PPAR delta. (C) 1999 Federation of European Biochemical Societies.