Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.

M.R. Soeters; M.J. Serlie; H.P. Sauerwein; M. Duran; J.P. de Ruiter; W. Kulik; M.T. Ackermans; P.E. Minkler; C.L. Hoppel; R.J. Wanders; S.M. Houten

doi:10.1016/j.metabol.2011.11.009

Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.

M.R. Soeters^*, M.J. Serlie, H.P. Sauerwein, M. Duran, J.P. de Ruiter, W. Kulik, M.T. Ackermans, P.E. Minkler, C.L. Hoppel, R.J. Wanders, S.M. Houten

^*Corresponding author for this work

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Abstract

Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid beta-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.

Original language	English
Pages (from-to)	966-973
Number of pages	8
Journal	Metabolism-Clinical and Experimental
Volume	61
Issue number	7
DOIs	https://doi.org/10.1016/j.metabol.2011.11.009
Publication status	Published - Jul 2012

Keywords

FATTY-ACID OXIDATION
KETONE-BODIES
MASS-SPECTROMETRY
LIPID-SYNTHESIS
RAT-LIVER
ACYL-COA
CARNITINE
L-(&)-3-HYDROXYBUTYRATE
L-3-HYDROXYBUTYRATE
QUANTIFICATION

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10.1016/j.metabol.2011.11.009

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Soeters, M. R., Serlie, M. J., Sauerwein, H. P., Duran, M., de Ruiter, J. P., Kulik, W., Ackermans, M. T., Minkler, P. E., Hoppel, C. L., Wanders, R. J., & Houten, S. M. (2012). Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite. Metabolism-Clinical and Experimental, 61(7), 966-973. https://doi.org/10.1016/j.metabol.2011.11.009

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title = "Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.",

abstract = "Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid beta-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.",

keywords = "FATTY-ACID OXIDATION, KETONE-BODIES, MASS-SPECTROMETRY, LIPID-SYNTHESIS, RAT-LIVER, ACYL-COA, CARNITINE, L-(&)-3-HYDROXYBUTYRATE, L-3-HYDROXYBUTYRATE, QUANTIFICATION",

author = "M.R. Soeters and M.J. Serlie and H.P. Sauerwein and M. Duran and {de Ruiter}, J.P. and W. Kulik and M.T. Ackermans and P.E. Minkler and C.L. Hoppel and R.J. Wanders and S.M. Houten",

year = "2012",

month = jul,

doi = "10.1016/j.metabol.2011.11.009",

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T1 - Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite.

AU - Soeters, M.R.

AU - Serlie, M.J.

AU - Sauerwein, H.P.

AU - Duran, M.

AU - de Ruiter, J.P.

AU - Kulik, W.

AU - Ackermans, M.T.

AU - Minkler, P.E.

AU - Hoppel, C.L.

AU - Wanders, R.J.

AU - Houten, S.M.

PY - 2012/7

Y1 - 2012/7

N2 - Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid beta-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.

AB - Hydroxybutyrylcarnitine (HB-carnitine) is a metabolite that has been associated with insulin resistance and type 2 diabetes mellitus. It is currently unknown whether HB-carnitine can be produced from D-3-hydroxybutyrate (D-3HB), a ketone body; but its formation from L-3-HB-CoA, a fatty acid beta-oxidation intermediate, is well established. We aimed to assess which stereoisomers of 3-HB-carnitine are present in vivo. Ketosis and increased fatty acid oxidation were induced in 12 lean healthy men by a 38-hour fasting period. The D-3HB kinetics (stable isotope technique) and stereoisomers of muscle 3-HB-carnitine (high-performance liquid chromatography/ultra-performance liquid chromatography-tandem mass spectrometry) were measured. Muscle D-3HB-carnitine content was much higher compared with L-3HB-carnitine. In addition, muscle D-3HB-carnitine correlated significantly with D-3-HB production. Following the finding that a ketone body can be converted into a carnitine ester in vivo, we show in vitro that D-3-HB can be converted into HB-carnitine (ketocarnitine) via an acyl-CoA synthetase reaction in several tissues including human muscle. During fasting, HB-carnitine in muscle is derived mainly from the ketone body D-3HB. The role of D-3HB-carnitine synthesis in metabolism remains to be elucidated.

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KW - KETONE-BODIES

KW - MASS-SPECTROMETRY

KW - LIPID-SYNTHESIS

KW - RAT-LIVER

KW - ACYL-COA

KW - CARNITINE

KW - L-(&)-3-HYDROXYBUTYRATE

KW - L-3-HYDROXYBUTYRATE

KW - QUANTIFICATION

U2 - 10.1016/j.metabol.2011.11.009

DO - 10.1016/j.metabol.2011.11.009

M3 - Article

C2 - 22209095

SN - 0026-0495

VL - 61

SP - 966

EP - 973

JO - Metabolism-Clinical and Experimental

JF - Metabolism-Clinical and Experimental

IS - 7

ER -