Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation.
BACKGROUND
Exercise 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.


RESULTS
First, 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% V(IAT)) or a 120 min run (at 70% V(IAT)) a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial beta-oxidation was verified in skeletal muscle cell culture experiments by probing (13)C-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.


CONCLUSIONS
Medium 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.
Lehmann
Rainer
R
Central Laboratory, Division of Clinical Chemistry and Pathobiochemistry, University Hospital Tuebingen, Tuebingen, Germany. Rainer.Lehmann@med.uni-tuebingen.de
Zhao
Xinjie
X
Weigert
Cora
C
Simon
Perikles
P
Fehrenbach
Elvira
E
Fritsche
Jens
J
Machann
Jürgen
J
Schick
Fritz
F
Wang
Jiangshan
J
Hoene
Miriam
M
Schleicher
Erwin D
ED
Häring
Hans-Ulrich
HU
Xu
Guowang
G
Niess
Andreas M
AM
D000328:Adult; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015444:Exercise / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction
C116917:acylcarnitine; D002331:Carnitine