The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.
The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.
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年龄和单侧腿部固定 2 周对人体骨骼肌中等强度运动期间基质利用率的影响。
DOI：
10.1113/jp271712
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Vigelsø A
中科院分区：
文献类型：
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作者：
Vigelsø A
本研究旨在从分子水平上揭示中等强度运动中年龄和体力活动不足对底物代谢调节的不同影响。运用动静脉平衡技术，研究双腿动态伸膝中等强度运动中单腿制动2周对青年和老年男子小腿底物利用的影响，以及运动前后肌肉代谢中关键蛋白质的变化。年龄和活动不影响运动中碳水化合物和脂肪的相对利用，但老年男子对外源脂肪酸的摄取较高。然而，年轻人在锻炼时更多地依赖内源性脂肪酸。使用全腿和分子相结合的方法，我们提供了证据，年龄和体力活动缺乏都会导致肌肉内脂肪积累，但这只是通过相同的机制发生的部分。摘要年龄和不活动与肌肉内甘油三酯(IMTG)积累有关。在这里，我们试图通过研究两周的单侧腿部制动对青年(n=17；23±0.11岁)和老年男性(n=1.15；68±0.11岁)在中等强度运动中腿部基质利用的影响来解开这些因素，并以对侧腿部作为对照。制动后，受试者在∼50%最大工作能力下进行双腿独立伸膝运动，训练强度为20±1.1W，持续45min，并将导管插入肱动脉和双侧股静脉。于运动前后取双腿股外侧肌活检标本，进行底物、蛋白质含量和酶活性分析。在运动期间，腿部底物利用(呼吸商)在不同组或不同腿部之间没有差异。老年人的腿部脂肪酸摄取比年轻男性更大，尽管年轻男性在运动中表现出腿部甘油的净释放，但老年男性表现出甘油的净摄取。在基础状态下，青年男性的肌甘油三酯、肌丙酮酸脱氢酶复合体活性、脂肪甘油三酯脂肪酶、乙酰辅酶A羧基酶2和腺苷活化蛋白激酶γ3的蛋白含量均高于老年男性。此外，青年和老年男性制动侧的脂肪甘油三酯脂肪酶、质膜相关脂肪酸结合蛋白和AMPKIMTG3亚单位蛋白含量均低于健侧，γ高于健侧。因此，在适度运动中，固定和年龄不影响底物选择(呼吸商)，但脂肪酸动员的整体和分子差异可以解释年龄和固定诱导的IMTG积累。
Key pointsThis study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate‐intensity exercise.Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two‐legged dynamic knee‐extensor moderate‐intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise.Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise.Using a combined whole‐leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms.AbstractAge and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate‐intensity exercise in young (n= 17; 23 ± 1 years old) and older men (n= 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two‐legged isolated knee‐extensor exercise at 20 ± 1 W (∼50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl‐CoA carboxylase 2 and AMP‐activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane‐associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole‐leg and molecular differences in fatty acid mobilization could explain the age‐ and immobilization‐induced IMTG accumulation.