Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity
Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity
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DOI：
10.1113/jphysiol.2003.045591
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发表时间：
2003-09-01
影响因子：
5.5
通讯作者：
Hamilton, MT
中科院分区：
文献类型：
--
作者：
Bey, L;Hamilton, MT
我们研究了在不运动时骨骼肌中脂蛋白脂肪酶（LPL）活性的调节，并将其与低强度的运动对照进行了比较。从急性阻止大鼠一个或两个后肢的运动活动的研究中，研究表明，在具有运动活动的大鼠肌肉中，正常存在的肝素释放（HR） LPL活性的90- 95%类似于丢失，因此依赖于局部收缩活动。同样，不同纤维类型肌肉之间LPL活动差异的95%依赖于运动活动。在许多大鼠和小鼠、两性、三种肌肉类型以及急性和慢性（1 - 1天）治疗期间，对不同的不运动模型进行的验证性研究表明，不运动显著降低肌肉LPL活动这一发现的稳健性是显而易见的。不运动导致肌肉对血浆[H-3]甘油三酯摄取的局部减少和高密度脂蛋白胆固醇浓度的降低。LPL mRNA的表达在动态对照组和急性或慢性不运动组之间没有差异。相反，该过程涉及通过放线菌素d敏感信号机制（即转录依赖过程）快速丢失HR-LPL蛋白质量（LPL主要与血管内皮相关的部分）。细胞内LPL蛋白含量的显著下降滞后于HR-LPL蛋白的损失。在不活动后4小时内，跑步机行走使LPL活性增加了8倍（P < 0.01）。肌肉LPL对不运动和低强度收缩活动的惊人敏感性可能提供了一个谜题，为什么不运动是代谢疾病的一个风险因素，为什么即使是不剧烈的运动也能显著地预防涉及脂质代谢不良的疾病。
We have examined the regulation of lipoprotein lipase (LPL) activity in skeletal muscle during physical inactivity in comparison to low-intensity contractile activity of ambulatory controls. From studies acutely preventing ambulatory activity of one or both the hindlimbs in rats, it was shown that similar to90-95 % of the heparin-releasable (HR) LPL activity normally present in rat muscle with ambulatory activity is lost, and thus dependent on local contractile activity. Similarly, similar to95 % of the differences in LPL activity between muscles of different fibre types was dependent on ambulatory activity. The robustness of the finding that physical inactivity significantly decreases muscle LPL activity was evident from confirmatory studies with different models of inactivity, in many rats and mice, both sexes, three muscle types and during both acute and chronic (I I days) treatment. Inactivity caused a local reduction of plasma [H-3] triglyceride uptake into muscle and a decrease in high density lipoprotein cholesterol concentration. LPL mRNA was not differentially expressed between ambulatory controls and either the acutely or chronically inactive groups. Instead, the process involved a rapid loss of the HR-LPL protein mass (the portion of LPL largely associated with the vascular endothelium) by an actinomycin D-sensitive signalling mechanism (i.e. transcriptionally dependent process). Significant decreases of intracellular LPL protein content lagged behind the loss of HR-LPL protein. Treadmill walking raised LPL activity similar to8-fold (P < 0.01) within 4 h after inactivity. The striking sensitivity of muscle LPL to inactivity and low-intensity contractile activity may provide one piece of the puzzle for why inactivity is a risk factor for metabolic diseases and why even non-vigorous activity provides marked protection against disorders involving poor lipid metabolism.