Abstract
Thyroid hormones are known to stimulate thermogenesis in rodents by exerting a permissive effect on norepinephrine that affects uncoupling protein-1 (UCP1) expression in brown adipose tissue (BAT). The aim of this study was to identify new targets of the thermogenic effects of T3 in tissues other than the BAT, such as skeletal muscle. In β1/β2/β3-adrenoceptor knockout (β-less) mice, that are dramatically cold intolerant, a normal body temperature was maintained throughout 48 h of cold exposure by T3 administration. In these mice, BAT UCP1 protein expression was not modified either by cold exposure or by T3 administration. To test the possibility that T3 might act via muscle uncoupling protein-3 (UCP3), an UCP3 knockout (KO) model was used. This model exhibited a normal phenotype except that, upon T3 administration, stimulated oxygen consumption of the UCP3KO mice was significantly lower by 6% than that of the wild-type (WT) mice. This difference was observed only during the dark period (between 7.00 p.m. and 7.00 a.m.), i.e. when the mice are the most active at consuming food. Therefore, UCP3 might participate in the correction by T3 of the dramatic cold intolerance of the β-less mice. These results reactivate the idea that UCP3 might play a role in the control of energy balance.
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Acknowledgements
This work was carried out thanks to the Swiss National Science Foundation Grants N° 3100AO-105889 and the European Community (EC) FP6 funding (to F.R.-J.), contract n° LSHM-CT-2003-503041. This study was part of the Geneva Programme for Metabolic Disorders. We are deeply indebted to Prof. Albert Burger for advice and helpful discussions and we thank Mrs. Françoise Kuhne for her excellent technical assistance. We are very grateful to Dr. Kobilka for providing us with the double KO mice.
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Pierre Flandin and Lorenz Lehr have contributed equally to this work.
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Flandin, P., Lehr, L., Asensio, C. et al. Uncoupling protein-3 as a molecular determinant of the action of 3,5,3′-triiodothyronine on energy metabolism. Endocr 36, 246–254 (2009). https://doi.org/10.1007/s12020-009-9217-8
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DOI: https://doi.org/10.1007/s12020-009-9217-8