2. Academic Validation
  3. Identification and regulation of the xenometabolite derivatives cis- and trans-3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans

Identification and regulation of the xenometabolite derivatives cis- and trans-3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans

  • Am J Physiol Endocrinol Metab. 2020 May 1;318(5):E701-E709. doi: 10.1152/ajpendo.00510.2019.
Hany F Sobhi 1,  Xinjie Zhao 2,  Peter Plomgaard 3 4 5,  Miriam Hoene 6,  Jakob S Hansen 3 4,  Benedikt Karus 7,  Andreas M Niess 7,  Hans U Häring 8 9,  Rainer Lehmann 6 8 9,  Sean H Adams 10 11,  Guowang Xu 2,  Cora Weigert 6 8 9
Affiliations

Affiliations

  • 1 Department of Natural Sciences, Center for Organic Synthesis, Coppin State University, Baltimore, Maryland.
  • 2 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Dalian, China.
  • 3 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
  • 4 The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases and CMRC, Rigshospitalet, Copenhagen, Denmark.
  • 5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 6 Institute for Clinical Chemistry and Pathobiochemistry, University Hospital, Tuebingen, Germany.
  • 7 Department for Sports Medicine, University Hospital, Tuebingen, Germany.
  • 8 Institute for Diabetes Research and Metabolic Diseases, Helmholtz Zentrum Muenchen, University of Tuebingen, Tuebingen, Germany.
  • 9 German Center for Diabetes Research, Oberschleissheim, Germany.
  • 10 Arkansas Children's Nutrition Center, Little Rock, Arkansas.
  • 11 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
PMID: 32101032 DOI: 10.1152/ajpendo.00510.2019
Abstract

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, cis-3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified trans-3,4-methylene-heptanoylcarnitine, and its cis-isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. We analyzed the regulation by exercise and the arterial-to-venous differences of these cyclopropane ring-containing carnitine esters over the hepatosplanchnic bed and the exercising leg in plasma samples obtained in three separate studies from young, lean and healthy males. Compared with other medium-chain acylcarnitines, the plasma concentrations of the 3,4-methylene-heptanoylcarnitine isomers only marginally increased with exercise. Both isomers showed a more than twofold increase in the skeletal muscle tissue of the exercising leg; this may have been due to the net effect of fatty acid oxidation in the exercising muscle and uptake from blood. The latter idea is supported by a more than twofold increased net uptake in the exercising leg only. Both isomers showed a constant release from the hepatosplanchnic bed, with an increased release of the trans-isomer after exercise. The isomers differ in their plasma concentration, with a four times higher concentration of the cis-isomer regardless of the exercise state. This is the first approach studying kinetics and fluxes of xenolipid isomers from tissues under exercise conditions, supporting the hypothesis that hepatic metabolism of cyclopropane ring-containing fatty acids is one source of these acylcarnitines in plasma. The data also provide clear evidence for an exercise-dependent regulation of xenometabolites, opening perspectives for future studies about the physiological role of this largely unknown class of metabolites.

Keywords

arterial-to-venous difference; exercise; liver; microbiome; xenolipids.

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