Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans

Abstract

Zhang J, Bhattacharyya S, Hickner RC, Light AR, Lambert CJ, Gale BK, Fiehn O, Adams SH. Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans. 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 O 2 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 ␣-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. beta-oxidation; interstitium; metabolome

Inflammatory Markers in Suction Blister Fluid: A Comparative Study Between Interstitial Fluid and Plasma

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Metabolomics and Lipidomics: Expanding the Molecular Landscape of Exercise Biology

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“…Out of 299 detected metabolites, only 43% were common to both biofluids. Among the 204 metabolites changed by exercise, only 20% were shared, therefore underscoring the limited ability of circulating metabolites to reflect the full range of muscle metabolic changes induced by exercise [ 101 ]. Additional pilot data from human muscle interstitial fluid was also collected in this study and, in line with rat data, reported increased TCA cycle intermediates following exercise, possibly induced by increased FA oxidation.…”

Flexibility of equine bioenergetics and muscle plasticity in response to different types of training: An integrative approach, questioning existing paradigms

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