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

PLoS ONE

Volumn 5, Issue 7, 2010, Pages

  Lehmann, Rainer ^a   Zhao, Xinjie ^b   Weigert, Cora ^a   Simon, Perikles ^c   Fehrenbach, Elvira ^a   Fritsche, Jens ^d   Machann, Jürgen ^a   Schick, Fritz ^a   Wang, Jiangshan ^b   Hoene, Miriam ^a   Schleicher, Erwin D ^a   Häring, Hans Ulrich ^a   Xu, Guowang ^b   Niess, Andreas M ^a  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b DALIAN INSTITUTE OF CHEMICAL PHYSICS   (China)

^c JOHANNES GUTENBERG UNIVERSITY   (Germany)

^d IMMATICS BIOTECHNOLOGIES GMBH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLCARNITINE; ANGIOPOIETIN; ANGIOPOIETIN LIKE 4; CARNITINE; CARNITINE PALMITOYLTRANSFERASE I; CARNITINE PALMITOYLTRANSFERASE IB; CD36 ANTIGEN; CYTOCHROME C OXIDASE; CYTOCHROME C OXIDASE SUBUNIT 1; DECANOYLCARNITINE; LAUROYLCARNITINE; LONG CHAIN ACYLCARNITINE; MEDIUM CHAIN ACYLCARNITINE; OCTANOYLCARNITINE; PALMITIC ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; UNCLASSIFIED DRUG; DRUG DERIVATIVE;

ADULT; AEROBIC EXERCISE; ANIMAL TISSUE; ARTICLE; BLOOD ANALYSIS; CONTROLLED STUDY; ENDURANCE TRAINING; EXERCISE INTENSITY; EXTENSOR DIGITORUM LONGUS MUSCLE; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN EXPERIMENT; LIPID OXIDATION; LIQUID CHROMATOGRAPHY; MALE; METABOLITE; METABOLOMICS; MOUSE; MYOTUBE; NONHUMAN; NORMAL HUMAN; QUADRICEPS FEMORIS MUSCLE; RUNNING; SKELETAL MUSCLE; SOLEUS MUSCLE; TIME OF FLIGHT MASS SPECTROMETRY; TREADMILL EXERCISE; ANIMAL; BLOOD; CELL CULTURE; CHEMISTRY; CLINICAL TRIAL; EXERCISE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; LIPID METABOLISM; MASS SPECTROMETRY; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OXIDATION REDUCTION REACTION; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ADULT; ANIMALS; CARNITINE; CELLS, CULTURED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; EXERCISE; HUMANS; LIPID METABOLISM; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MASS SPECTROMETRY; MICE; MUSCLE FIBERS, SKELETAL; MUSCLE, SKELETAL; OXIDATION-REDUCTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 77955399279     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0011519     Document Type: Article

References (53)

1. Ivy JL (1997) Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med 24: 321-336.
2. Olsen RH, Krogh-Madsen R, Thomsen C, Booth FW, Pedersen BK (2008) Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA 299: 1261-1263.
3. Dela F, Kjaer M (2006) Resistance training, insulin sensitivity and muscle function in the elderly. Essays Biochem 42: 75-88.
4. Kiens B, Essen-Gustavsson B, Christensen NJ, Saltin B (1993) Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training. J Physiol 469: 459-478.
5. Mourtzakis M, Saltin B, Graham T, Pilegaard H (2006) Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids. J Appl Physiol 100: 1822-1830.
6. Turcotte LP, Richter EA, Kiens B (1992) Increased plasma FFA uptake and oxidation during prolonged exercise in trained vs. untrained humans. Am J Physiol 262: E791-E799.
7. Spriet LL, Watt MJ (2003) Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise. Acta Physiol Scand 178: 443-452.
8. Burke LM, Hawley JA (2006) Fat and carbohydrate for exercise. Curr Opin Clin Nutr Metab Care 9: 476-481.
9. Hurley BF, Nemeth PM, Martin WH, III, Hagberg JM, Dalsky GP, et al. (1986) Muscle triglyceride utilization during exercise: effect of training. J Appl Physiol 60: 562-567.
10. Coggan AR, Kohrt WM, Spina RJ, Bier DM, Holloszy JO (1990) Endurance training decreases plasma glucose turnover and oxidation during moderateintensity exercise in men. J Appl Physiol 68: 990-996.
11. Martin WH, III, Dalsky GP, Hurley BF, Matthews DE, Bier DM, et al. (1993) Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise. Am J Physiol 265: E708-E714.
12. Pedersen BK, Akerstrom TC, Nielsen AR, Fischer CP (2007) Role of myokines in exercise and metabolism. J Appl Physiol. pp 1093-1098.
13. Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, et al. (2008) Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134: 933-944.
14. Lindon JC, Holmes E, Bollard ME, Stanley EG, Nicholson JK (2004) Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers 9: 1-31.
15. Lenz EM, Wilson ID (2007) Analytical strategies in metabonomics. J Proteome Res 6: 443-458.
16. Zhao X, Peter A, Fritsche J, Elcnerova M, Fritsche A, et al. (2009) Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at? Am J Physiol Endocrinol Metab 296: E384-E393.
17. Wu Z, Huang Z, Lehmann R, Zhao C, Xu G (2009) The Application of Chromatography-Mass Spectrometry: Methods to Metabonomics. Chromatographia 69: S23-S32.
18. Wang-Sattler R, Yu Y, Mittelstrass K, Lattka E, Altmaier E, et al. (2008) Metabolic profiling reveals distinct variations linked to nicotine consumption in humans-first results from the KORA study. PLoS One 3: e3863.
19. Pohjanen E, Thysell E, Jonsson P, Eklund C, Silfver A, et al. (2007) A multivariate screening strategy for investigating metabolic effects of strenuous physical exercise in human serum. J Proteome Res 6: 2113-2120.
20. Yan BAJ, Wang G, Lu H, Huang X, et al. (2009) Metabolomic investigation into variation of endogenous metabolites in professional athletes subject to strengthendurance training. J Appl Physiol 106: 531-538.
21. Chorell E, Moritz T, Branth S, Antti H, Svensson M (2009) A predictive metabolomics evaluation of nutrition-modulated metabolic stress responses in human blood serum during the early recovery phase of strenuous physical exercise. J Proteome Res 8: 2966-2977.
22. Enea C, Seguin F, Petitpas-Mulliez J, Boildieu N, Boisseau N, et al. (2010) (1)HNMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise. Anal Bioanal Chem 396: 1167-1176.
23. Spurway NC (1992) Aerobic exercise, anaerobic exercise and the lactate threshold. Br Med Bull 48: 569-591.
24. Wold S, Antti H, Lindgren F, Ohman J (1998) Orthogonal signal correction of near-infrared spectra. Chemometrics Intell Lab Syst 44: 175-185.
25. Eriksson L, Johansson E, Kettaneh-Wold N, Wold S (2001) Multi- and megavariate data analysis principals and applications Umetrics, Umea, Sweden.
26. Wiklund S, Johansson E, Sjostrom L, Mellerowicz EJ, Edlund U, et al. (2008) Visualization of GC/TOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models. Anal Chem 80: 115-122.
27. Friolet R, Hoppeler H, Krahenbuhl S (1994) Relationship between the coenzyme A and the carnitine pools in human skeletal muscle at rest and after exhaustive exercise under normoxic and acutely hypoxic conditions. J Clin Invest 94: 1490-1495.
28. Hiatt WR, Regensteiner JG, Wolfel EE, Ruff L, Brass EP (1989) Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state. J Clin Invest 84: 1167-1173.
29. Carlin JI, Reddan WG, Sanjak M, Hodach R (1986) Carnitine metabolism during prolonged exercise and recovery in humans. J Appl Physiol 61: 1275-1278.
30. Lennon DL, Stratman FW, Shrago E, Nagle FJ, Madden M, et al. (1983) Effects of acute moderate-intensity exercise on carnitine metabolism in men and women. J Appl Physiol 55: 489-495.
31. Stephens FB, Constantin-Teodosiu D, Greenhaff PL (2007) New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol 581: 431-444.
32. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, et al. (2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 7: 45-56.
33. Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, et al. (2009) Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control. J Biol Chem 284: 22840-22852.
34. Ramsay RR, Zammit VA (2004) Carnitine acyltransferases and their influence on CoA pools in health and disease. Mol Aspects Med 25: 475-493.
35. Bennett MJ (1994) The enzymes of mitochondrial fatty acid oxidation. Clin Chim Acta 226: 211-224.
36. Hoppel C (2003) The role of carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 41: S4-12.
37. Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, et al. (2010) Increased Levels of Plasma Acylcarnitines in Obesity and Type 2 Diabetes and Identification of a Marker of Glucolipotoxicity. Obesity (Silver Spring).
38. Soeters MR, Sauerwein HP, Duran M, Wanders RJ, Ackermans MT, et al. (2009) Muscle acylcarnitines during short-term fasting in lean healthy men. Clin Sci (Lond) 116: 585-592.
39. Sahlin K (1990) Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand 138: 259-262.
40. Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, et al. (1998) Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 273: 20378-20382.
41. Tamai I, Ohashi R, Nezu JI, Sai Y, Kobayashi D, et al. (2000) Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem 275: 40064-40072.
42. Stanley CA, DeLeeuw S, Coates PM, Vianey-Liaud C, Divry P, et al. (1991) Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann Neurol 30: 709-716.
43. Pande SV, Parvin R (1976) Characterization of carnitine acylcarnitine translocase system of heart mitochondria. J Biol Chem 251: 6683-6691.
44. Oram JF, Wenger JI, Neely JR (1975) Regulation of long chain fatty acid activation in heart muscle. J Biol Chem 250: 73-78.
45. Zhang Z, Zhao M, Li Q, Zhao H, Wang J, et al. (2009) Acetyl-l-carnitine inhibits TNF-alpha-induced insulin resistance via AMPK pathway in rat skeletal muscle cells. FEBS Lett 583: 470-474.
46. Ho JK, Duclos RI, Jr., Hamilton JA (2002) Interactions of acyl carnitines with model membranes: a (13)C-NMR study. J Lipid Res 43: 1429-1439.
47. Dickhuth HH, Huonker M, Muenzel T, Drexler H, Berg A, Keul J (1991) Individual threshold for evaluation of competitive athletes and patients with left ventricular dysfunction. In: Advances in Ergometry (N Bachl, TE Graham, H Loellgen), eds. pp 73-79. Springer, Berlin.
48. McConnell TR (1988) Practical considerations in the testing of VO2max in runners. Sports Med 5: 57-68.
49. Thamer C, Machann J, Bachmann O, Haap M, Dahl D, et al. (2003) Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity. J Clin Endocrinol Metab 88: 1785-1791.
50. Weigert C, Brodbeck K, Staiger H, Kausch C, Machicao F, et al. (2004) Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factorkappaB. J Biol Chem 279: 23942-23952.
51. Chen J, Zhao X, Fritsche J, Yin P, Schmitt-Kopplin P, et al. (2008) Practical approach for the identification and isomer elucidation of biomarkers detected in a metabonomic study for the discovery of individuals at risk for diabetes by integrating the chromatographic and mass spectrometric information. Anal Chem 80: 1280-1289.
52. Hodson MP, Dear GJ, Roberts AD, Haylock CL, Ball RJ, et al. (2007) A genderspecific discriminator in Sprague-Dawley rat urine: the deployment of a metabolic profiling strategy for biomarker discovery and identification. Anal Biochem 362: 182-192.
53. Bijlsma S, Bobeldijk I, Verheij ER, Ramaker R, Kochhar S, et al. (2006) Largescale human metabolomics studies: a strategy for data (pre-) processing and validation. Anal Chem 78: 567-574.