Yoshitomi H, Yamazaki K, Abe S, Tanaka I
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Biochem Biophys Res Commun. 1998 Dec 9;253(1):85-91. doi: 10.1006/bbrc.1998.9746.
Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters that dissipate the proton gradient, releasing stored energy as heat, without coupling to other energy-consuming processes. Therefore, the UCPs are thought to be important determinants of the metabolic efficiency. To elucidate relationships between the UCPs expressions and insulin sensitivity improvement, we treated KK-Ay mice with beta 3 adrenergic receptor agonist for 21 days and examined the changes of the UCPs mRNA expressions in various tissues. Chronic treatment of a specific beta 3 adrenergic receptor agonist, CL316,243 (0.2 mg/kg body weight/day s.c.) markedly increased the expressions of uncoupling protein 1 (UCP1), uncoupling protein 2 (UCP2), and uncoupling protein 3 (UCP3) by 14-fold, 6-fold, and 16-fold, respectively, in the brown adipose tissue (BAT). The UCP1 and UCP3 mRNA expressions in the white adipose tissue (WAT) were also increased by 12-fold and 9-fold, respectively, but the UCP2 mRNA expression was not changed in this tissue. Interestingly, the UCP2 and UCP3 mRNA expressions were strikingly decreased in the skeletal muscle and heart. Particularly, the UCP3 mRNA expression level in the skeletal muscle was dropped to 10% of that of the saline-treated control mice, indicating that the UCPs mRNA expressions are regulated in tissue-specific ways. The concentrations of plasma insulin and circulating free fatty acid (FFA) were significantly decreased, suggesting that they correlate with the reductions of the UCP2 and UCP3 mRNA expressions in the skeletal muscle and heart. It has been thought that the UCP1 and UCP3 mRNA expressions in the BAT and WAT are mainly controlled by the hypothalamus via the sympathetic nervous system, while the levels of insulin, FFA or both may play important roles in the control of the UCP2 and UCP3 mRNA expressions in the skeletal muscle an heart.
解偶联蛋白（UCPs）是线粒体内膜转运蛋白，可消耗质子梯度，将储存的能量以热量形式释放，而不与其他耗能过程偶联。因此，UCPs被认为是代谢效率的重要决定因素。为了阐明UCPs表达与胰岛素敏感性改善之间的关系，我们用β3肾上腺素能受体激动剂治疗KK-Ay小鼠21天，并检测了各种组织中UCPs mRNA表达的变化。长期给予特定的β3肾上腺素能受体激动剂CL316,243（0.2 mg/kg体重/天，皮下注射）可使棕色脂肪组织（BAT）中的解偶联蛋白1（UCP1）、解偶联蛋白2（UCP2）和解偶联蛋白3（UCP3）的表达分别显著增加14倍、6倍和16倍。白色脂肪组织（WAT）中的UCP1和UCP3 mRNA表达也分别增加了12倍和9倍，但该组织中的UCP2 mRNA表达未发生变化。有趣的是，骨骼肌和心脏中的UCP2和UCP3 mRNA表达显著降低。特别是，骨骼肌中UCP3 mRNA表达水平降至生理盐水处理的对照小鼠的10%，表明UCPs mRNA表达是以组织特异性方式调节的。血浆胰岛素和循环游离脂肪酸（FFA）浓度显著降低，表明它们与骨骼肌和心脏中UCP2和UCP3 mRNA表达的降低相关。一直以来人们认为，BAT和WAT中UCP1和UCP3 mRNA表达主要由下丘脑通过交感神经系统控制，而胰岛素、FFA或两者的水平可能在控制骨骼肌和心脏中UCP2和UCP3 mRNA表达方面发挥重要作用。
