Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle

Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
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DOI:
10.1172/jci11775
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发表时间:
2001-09-01
影响因子:
15.9
通讯作者:
Shulman, GI
Shulman, GI
中科院分区:
医学1区
文献类型:
--
作者:
Lebon, V;Dufour, S;Shulman, GI

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甲状腺激素调节基础代谢率的机制尚不清楚。虽然有人认为甲状腺激素可能使底物氧化与ATP合成分离,但没有来自人类研究的数据支持这一假设。为了检验这种可能性,我们使用一种新型的C-13/P-31核磁共振(NMR)联合方法来评估七名健康成年人在三碘甲状腺原氨酸(T-3)治疗三天之前和之后骨骼肌中的线粒体能量耦合。ATP合成速率和三羧酸(TCA)循环通量分别通过P-31和C-13 NMR光谱测量,并评估线粒体能量耦合的比例。T-3治疗后,肌肉TCA循环通量增加约70%。相反,ATP合成速率保持不变。考虑到TCA循环通量与ATP合成相比不成比例的增加,这些数据表明T-3部分通过促进骨骼肌中线粒体能量解偶联来促进产热增加。
The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP synthesis, there are no data from studies on humans to support this hypothesis. To examine this possibility, we used a novel combined C-13/P-31 nuclear magnetic resonance (NMR) approach to assess mitochondrial energy coupling in skeletal muscle of seven healthy adults before and after three days of triiodothyronine (T-3) treatment. Rates of ATP synthesis and tricarboxylic acid (TCA) cycle fluxes were measured by P-31 and C-13 NMR spectroscopy, respectively, and mitochondrial energy coupling was assessed as the ratio. Muscle TCA cycle flux increased by approximately 70% following T-3 treatment. In contrast, the rate of ATP synthesis remained unchanged. Given the disproportionate increase in TCA cycle flux compared with ATP synthesis, these data suggest that T-3 promotes increased thermogenesis in part by promoting mitochondrial energy uncoupling in skeletal muscle.