Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans.
Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans.
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DOI：
10.1152/ajpendo.00156.2018
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发表时间：
2019-01
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影响因子：
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通讯作者：
Jie Zhang;S. Bhattacharyya;R. Hickner;A. Light;Christopher J. Lambert;B. Gale;O. Fiehn;S. Adams
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文献类型：
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作者：
Jie Zhang;S. Bhattacharyya;R. Hickner;A. Light;Christopher J. Lambert;B. Gale;O. Fiehn;S. Adams
血液或活组织检查通常用于表征运动肌肉调节的代谢物。然而，血液输入来自多种组织，活检无法区分分泌代谢物和细胞内代谢物，而且它们的侵入性对于敏感人群的频繁采集来说具有挑战性（例如，儿童和孕妇）。因此，间质液（IF）代谢组学的微创方法将是有价值的。设计了一种导管，用于在休息时或运动20分钟后立即从急性麻醉的成年雄性大鼠的腓肠肌中收集IF（约60%的最大O2摄取量）。非靶向，气相色谱-飞行时间质谱分析用于检测299种代谢物，包括未注释的代谢物，糖，脂肪酸，氨基酸和嘌呤代谢物和衍生物。在所有检测到的代谢物中，只有43%是IF和血浆共有的，只有20%的运动修饰代谢物在两个池中共享，这表明血液并不能完全反映肌肉中的代谢结果。值得注意的运动模式包括IF氨基酸增加（亮氨酸和异亮氨酸除外）、α-酮戊二酸和柠檬酸增加（可能反映三羧酸分解或非线粒体途径的变化）以及信号脂质油酰胺浓度升高。使用20 kDa的微透析导管放置在股外侧肌的5名健康成年人在休息和运动期间（65%的估计最大心率）的人肌肉IF进行了初步研究。大约70%的通常检测到的代谢物区分休息与运动在大鼠中也发生了变化。间质代谢组学可以帮助识别信号肌肉工作的分子（例如，运动和疲劳）和肌肉健康。
Blood or biopsies are often used to characterize metabolites that are modulated by exercising muscle. However, blood has inputs derived from multiple tissues, biopsies cannot discriminate between secreted and intracellular metabolites, and their invasive nature is challenging for frequent collections in sensitive populations (e.g., children and pregnant women). Thus, minimally invasive approaches to interstitial fluid (IF) metabolomics would be valuable. A catheter was designed to collect IF from the gastrocnemius muscle of acutely anesthetized adult male rats at rest or immediately following 20 min of exercise (~60% of maximal O2 uptake). Nontargeted, gas chromatography-time-of-flight mass spectrometry analysis was used to detect 299 metabolites, including nonannotated metabolites, sugars, fatty acids, amino acids, and purine metabolites and derivatives. Just 43% of all detected metabolites were common to IF and blood plasma, and only 20% of exercise-modified metabolites were shared in both pools, highlighting that the blood does not fully reflect the metabolic outcomes in muscle. Notable exercise patterns included increased IF amino acids (except leucine and isoleucine), increased α-ketoglutarate and citrate (which may reflect tricarboxylic acid cataplerosis or shifts in nonmitochondrial pathways), and higher concentration of the signaling lipid oleamide. A preliminary study of human muscle IF was conducted using a 20-kDa microdialysis catheter placed in the vastus lateralis of five healthy adults at rest and during exercise (65% of estimated maximal heart rate). Approximately 70% of commonly detected metabolites discriminating rest vs. exercise in rats were also changed in exercising humans. Interstitium metabolomics may aid in the identification of molecules that signal muscle work (e.g., exertion and fatigue) and muscle health.