Medium Chain Acylcarnitines Dominate the Metabolite Pattern in Humans under Moderate Intensity Exercise and Support Lipid Oxidation

Abstract

BackgroundExercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise.Methodology and Principal FindingsFirst, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT-) metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% VIAT) or a 120 min run (at 70% VIAT) a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial β-oxidation was verified in skeletal muscle cell culture experiments by probing 13C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine.ConclusionsMedium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

A Metabolomics-driven Elucidation of the Anti-obesity Mechanisms of Xanthohumol

“…Plasma ACs increase during exercise due to an elevation in fatty acid supported respiration in muscle (57). Again in agreement with a state of acutely increased respiration, we observed modest increases in both acetylcarnitine and long chain ACs in the first 4 h post treatment.…”

Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

“…Plasma concentrations of acylcarnitines are not only a useful diagnostic marker to detect disorders in mitochondrial fatty acid oxidation but also reflect physiological changes in fatty acid oxidation flux [28][29][30]. Since the exercise-induced increase in short-, medium-and long-chain acylcarnitines was not different between the control group and the diabetic group, we conclude that the metabolic flexibility of diabetic individuals to enhance fat oxidation during acute exercise is not impaired.…”

Non-targeted metabolomics in sport and exercise science

“…In addition to products of fatty acid oxidation, induced changes of fatty acid transporter molecules have been measured through increases in medium to long-chain acylcarnitines which have been demonstrated to increase palmitate oxidation in isolated rat muscle (Krug et al, 2012;Lehmann et al, 2010;. Such measurement of circulating oxidation products and their transporter molecules could show utility in a medical setting, with cardiovascular disease conditions known to display alterations in cardiac tissue metabolism through dysregulated substrate utilisation (e.g.…”