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Wolf, M.* ; Chen, S.* ; Zhao, X.* ; Scheler, M. ; Irmler, M. ; Staiger, H. ; Beckers, J. ; Hrabě de Angelis, M. ; Fritsche, A. ; Häring, H.-U. ; Schleicher, E.D. ; Xu, G.* ; Lehmann, R. ; Weigert, C.

Production and release of acylcarnitines by primary myotubes reflect the differences in fasting fat oxidation of the donors.

J. Clin. Endocrinol. Metab. 98, E1137-E1142 (2013)
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Context:Acylcarnitines are biomarkers of incomplete β-oxidation and mitochondrial lipid overload but indicate also high rates of mitochondrial fatty acid oxidation. It is unknown whether the production of acylcarnitines in primary human myotubes obtained from lean, metabolically healthy subjects reflects the fat oxidation in vivo.Objective:Our objective was to quantify the acylcarnitine production in myotubes obtained from subjects with low and high fasting respiratory quotient (RQ).Methods:Fasting RQ was determined by indirect calorimetry. Muscle biopsies from the vastus lateralis muscle were taken from 6 subjects with low fasting RQ (mean 0.79 ± 0.03) and 6 with high fasting RQ (0.90 ± 0.03), and satellite cells were isolated, cultured, and differentiated to myotubes. Myotubes were cultivated with 125μM 13C-labeled palmitate for 30 minutes and 4 and 24 hours. Quantitative profiling of 42 intracellular and 31 extracellular acylcarnitines was performed by stable isotope dilution-based metabolomics analysis by liquid chromatography coupled to mass spectrometry.Results:Myotubes from donors with high fasting RQ produced and released significant higher amounts of medium-chain acylcarnitines. High 13C8 and 13C10 acylcarnitine levels in the extracellular compartment correlated with high fasting RQ. The decreased expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD) in these myotubes can explain the higher rate of incomplete fatty acid oxidation. A lower intracellular [13C]acetylcarnitine to carnitine and lower intracellular 13C16/13C18 acylcarnitine to carnitine ratio indicate reduced fatty acid oxidation capacity in these myotubes. Mitochondrial DNA content was not different.Conclusion:Acylcarnitine production and release from primary human myotubes of donors with high fasting RQ indicate a reduced fatty acid oxidation capacity and a higher rate of incomplete fatty acid oxidation. Thus, quantitative profiling of acylcarnitine production in human myotubes can be a suitable tool to identify muscular determinants of fat oxidation in vivo.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Intramyocellular Lipid-content ; Tandem Mass-spectrometry ; Skeletal-muscle ; Insulin-resistance ; Carnitine Metabolism ; Mcad Deficiency ; Blood Spots ; Weight-gain ; Obesity ; Acid
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Zeitschrift Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Band: 98, Heft: 6, Seiten: E1137-E1142 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)