Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle
Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle
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DOI：
10.1152/japplphysiol.00539.2021
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发表时间：
2022-02-01
影响因子：
3.3
通讯作者：
Hayashi, Tatsuya
中科院分区：
文献类型：
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作者：
Egawa, Tatsuro;Ogawa, Takeshi;Hayashi, Tatsuya
耐力运动触发骨骼肌适应，包括增强胰岛素信号、葡萄糖代谢和线粒体生物发生。然而，在某些情况下，运动诱导的骨骼肌适应可能不会发生，这种情况被称为运动阻力。甲基乙二醛（MG）是一种高活性的二羰基代谢物，对身体有不利影响，如引起糖尿病并发症、线粒体功能障碍和炎症。本研究旨在阐明甲基乙二醛对耐力运动后骨骼肌分子适应的影响。将小鼠随机分为4组（n = 12/组）：久坐对照组、自愿运动组、mg治疗组、mg治疗加自愿运动组。自愿运动组的小鼠被安置在一个带跑步轮的笼子里，而MG处理组的小鼠则饮用含有1% MG的水。四周的自愿运动诱导了跖肌中的几种分子适应，包括过氧化物酶体增殖体激活受体γ辅助激活因子1a （PGC1a）、线粒体复合体蛋白、toll样受体4 （TLR4）、72-kDa热休克蛋白（HSP72）、己糖激酶II和乙二醛酶1的表达增加；这也增强了胰岛素刺激的Akt Ser473磷酸化和柠檬酸合成酶活性。然而，MG处理抑制了这些适应性。在比目鱼肌中，运动诱导的TLR4、HSP72和晚期糖基化终产物受体1的表达增加在MG处理下被抑制。这些发现表明，MG是抑制耐力运动诱导的分子反应的一个因素，包括线粒体适应、胰岛素信号激活和几种与线粒体生物发生、葡萄糖处理和糖基化相关的蛋白质的上调，这些蛋白质主要是快速抽搐骨骼肌。这项研究调查了甲基乙二醛对耐力运动后骨骼肌适应的影响，甲基乙二醛是一种高活性羰基代谢物，对身体有有害影响。本研究的证据表明，甲基乙二醛是主要是快速抽搐骨骼肌对耐力运动反应性恶化的一个因素。
Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into four groups (n = 12/group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, whereas mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1a (PGC1a), mitochondria complex proteins, Toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle.NEW & NOTEWORTHY This study investigated the effect of methylglyoxal, which is a highly reactive carbonyl metabolite and has detrimental effects on the body, on skeletal muscle adaptations following endurance exercise. Evidences from this study show that methylglyoxal is a factor deteriorating responsiveness to endurance exercise in primarily fast-twitch skeletal muscle.