Fasting, lipid metabolism, and triiodothyronine in rat gastrocnemius muscle: interrelated roles of uncoupling protein 3, mitochondrial thioesterase, and coenzyme Q
Fasting, lipid metabolism, and triiodothyronine in rat gastrocnemius muscle: interrelated roles of uncoupling protein 3, mitochondrial thioesterase, and coenzyme Q
复制标题
DOI：
10.1096/fj.02-0839fje
复制
发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Goglia, F
中科院分区：
文献类型：
--
作者：
Moreno, M;Lombardi, A;Goglia, F
我们研究了禁食期间解偶联蛋白 3 (UCP3) 的作用，并检查了在这种情况下施用三碘甲状腺原氨酸 (T3) 的效果。还检查了线粒体硫酯酶 (MTE I) 的可能参与以及假定的辅因子（例如辅酶 Q (CoQ)）的作用。在这里，我们报告说，禁食诱导 MTE I 的表达和活性增加两倍以上，以及 UCP3 表达增加，但没有任何相关的解偶联活性。给禁食大鼠施用 T3 进一步上调 UCP3 和 MTE I 表达，显着增强 MTE I 酶活性，并防止禁食期间通常出现的 UCP3 解偶联活性受损。事实上，T3 处理诱导了 UCP3 依赖性的线粒体膜电位降低，通过添加 GDP 或超氧化物歧化酶 (SOD) 可以消除这种降低。 T3 给药还阻止了在禁食大鼠中观察到的 CoQ 水平的显着下降，这也提供了证据表明，在体内，CoQ 是 UCP3 介导的解偶联的重要辅助因子。数据还表明，MTE I 和 UCP3 可能参与相同的生化机制，并且 UCP3 假定的功能（例如脂质处理和解偶联）并不相互排斥，而是可能在体内共存。
We investigated the role of uncoupling protein 3 (UCP3) during fasting and examined the effect of triiodothyronine (T3) administration in such a condition. The possible involvement of mitochondrial thioesterase (MTE I) and the role of putative cofactors, such as coenzyme Q (CoQ), was also examined. Here, we report that fasting induced a more than twofold elevation in the expression and activity of MTE I, and an increase in UCP3 expression, without any associated uncoupling activity. Administration of T3 to fasting rats further up-regulated UCP3 as well as MTE I expression, markedly enhanced MTE I enzyme activity and prevented the impairment of the uncoupling activity of UCP3 normally seen during fasting. Indeed, T3-treatment induced an UCP3-dependent decrease in mitochondrial membrane potential, which was abolished by the addition of either GDP or superoxide dismutase (SOD). T3 administration also prevented the marked decrease of CoQ levels observed in fasting rats and this provides evidence that also, in vivo, CoQ represents an essential cofactor for the UCP3-mediated uncoupling. The data also show that MTE I and UCP3 are likely involved in the same biochemical mechanism and that UCP3 postulated functions, such as lipid handling and uncoupling, are not mutually exclusive but may coexist in vivo.