Uncoupling protein-3 as a molecular determinant of the action of 3,5,3'-triiodothyronine on energy metabolism.
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 beta(1)/beta(2)/beta(3)-adrenoceptor knockout (beta-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 beta-less mice. These results reactivate the idea that UCP3 might play a role in the control of energy balance.
Flandin
Pierre
P
Department of Cell Physiology and Metabolism, Medical University Centre, Geneva, Switzerland.
Lehr
Lorenz
L
Asensio
Cedric
C
Giacobino
Jean-Paul
JP
Rohner-Jeanrenaud
Françoise
F
Muzzin
Patrick
P
Jimenez
Maria
M
D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000502:physiology; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology* / Q000502:physiology; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3
D007473:Ion Channels; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; C000604372:Ucp1 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; D014284:Triiodothyronine