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

Lehmann R, Zhao X, Weigert C, Simon P, Fehrenbach E, Fritsche J, Machann J, Schick F, Wang J, Hoene M, Schleicher ED, Häring HU, Xu G, Niess AM - PLoS ONE (2010)

Bottom Line: 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.This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

View Article: PubMed Central - PubMed

Affiliation: Central Laboratory, Division of Clinical Chemistry and Pathobiochemistry, University Hospital Tuebingen, Tuebingen, Germany. Rainer.Lehmann@med.uni-tuebingen.de

ABSTRACT

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.

Methodology and principal findings: 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.

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Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *p<0.05, significantly different from the pre run signal intensity; (n = 13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% VIAT in an independent second exercise study. Values are means ±SE. *p<0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.
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pone-0011519-g002: Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *p<0.05, significantly different from the pre run signal intensity; (n = 13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% VIAT in an independent second exercise study. Values are means ±SE. *p<0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.

Mentions: The signal intensities (based on the peak height) of all acylcarnitines detectable in our mass spectrometric data showed similar kinetics, namely a strong, significant increase immediately after the exercise bout and a pronounced decrease thereafter leading to signal intensities similar to the pre-run data, except for C2:0(acetyl)-, C4:0(iso/butyryl)-, C12:1- and C14:0-carnitine, which showed no significant changes at any time point (Figure 2A). Exemplarily, the time course of C10:0-carnitine is presented in Figure 2B for each individual runner.


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

Lehmann R, Zhao X, Weigert C, Simon P, Fehrenbach E, Fritsche J, Machann J, Schick F, Wang J, Hoene M, Schleicher ED, Häring HU, Xu G, Niess AM - PLoS ONE (2010)

Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *p<0.05, significantly different from the pre run signal intensity; (n = 13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% VIAT in an independent second exercise study. Values are means ±SE. *p<0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2902514&req=5

pone-0011519-g002: Time-course for the acylcarnitine species plasma levels during the exercise phase and under recovery conditions.(A) Time-dependent changes of acylcarnitine species during the exercise bout and in the recovery phase, based on non-targeted (NT-)metabolomics signal intensity data. The relative amounts of acylcarnitines are based on peak heights. Values are means ±SE. *p<0.05, significantly different from the pre run signal intensity; (n = 13). (B) Time-dependent changes of 13 individual C10:0 carnitine levels based on NT-metabolomics data. (C) Quantitative analysis of time-dependent changes of plasma acylcarnitine concentrations investigated in eight individuals performing a continuous 120 min treadmill run at 70% VIAT in an independent second exercise study. Values are means ±SE. *p<0.05, significantly different from the pre-run concentrations. As a C8- instead of a C18-reversed phase UPLC-column was used to achieve the detection of the long-chain C16 (palmitoyl)-carnitine, the analysis of C2:0-carnitine was not possible in this experiment.
Mentions: The signal intensities (based on the peak height) of all acylcarnitines detectable in our mass spectrometric data showed similar kinetics, namely a strong, significant increase immediately after the exercise bout and a pronounced decrease thereafter leading to signal intensities similar to the pre-run data, except for C2:0(acetyl)-, C4:0(iso/butyryl)-, C12:1- and C14:0-carnitine, which showed no significant changes at any time point (Figure 2A). Exemplarily, the time course of C10:0-carnitine is presented in Figure 2B for each individual runner.

Bottom Line: 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.This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.

View Article: PubMed Central - PubMed

Affiliation: Central Laboratory, Division of Clinical Chemistry and Pathobiochemistry, University Hospital Tuebingen, Tuebingen, Germany. Rainer.Lehmann@med.uni-tuebingen.de

ABSTRACT

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.

Methodology and principal findings: 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.

Show MeSH