Bidirectional regulation of uncoupling protein-3 and GLUT-4 mRNA in skeletal muscle by cold.

To elucidate the possible role of the mitochondrial uncoupling protein (UCP)-3 in skeletal muscle as a regulator of adaptive thermogenesis and energy balance, we examined the modulation by cold exposure (5 degrees C) of UCP-3 and glucose transporter isoform GLUT-4 mRNAs in male Sprague-Dawley rats. In skeletal muscle, UCP-3 and GLUT-4 mRNAs increased two- to threefold between 6 and 24 h of cold exposure and then decreased to 50% of the control value after 6 days in the cold. In contrast, skeletal muscle UCP-2 mRNA showed a small increase on day 3 and returned to normal after 6 days. The bidirectional regulation of UCP-3 and GLUT-4 mRNAs in skeletal muscle by cold suggests that UCP-3 may be a major mediator of acute adaptive thermogenesis but then is downregulated, along with GLUT-4, in the chronic state to preserve energy. In contrast, cold exposure caused only transient changes of UCP-2 and GLUT-4 mRNA in heart. These data are consistent with the necessity of the heart to continuously expend energy to maintain blood circulation, regardless of environmental conditions.