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Am J Physiol Heart Circ Physiol 285: H1626-H1631, 2003; doi:10.1152/ajpheart.00332.2003
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{beta}-Hydroxybutyrate inhibits myocardial fatty acid oxidation in vivo independent of changes in malonyl-CoA content

William C. Stanley,1 Steven R. Meadows,1 Krista M. Kivilo,1 Bridgette A. Roth,1 and Gary D. Lopaschuk2

1Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970; and 2Cardiovascular Disease Research Group and Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2

Submitted 13 May 2003 ; accepted in final form 16 June 2003

This study tested the hypothesis that an acute infusion of {beta}-hydroxybutyrate inhibits myocardial fatty acid uptake and oxidation in vivo. Anesthetized pigs were untreated (n = 6) or treated with an intravenous infusion of fat emulsion (n = 7) to elevate plasma free fatty acid levels. A third group received fat emulsion plus an intravenous infusion of {beta}-hydroxybutyrate (25 µmol·kg–1·min–1; n = 7) for 60 min. All animals received a continuous infusion of [3H]palmitate, and myocardial fatty acid oxidation was measured from the cardiac production of 3H2O. Plasma free fatty acid concentrations were elevated in the fat emulsion group (0.77 ± 0.11 mM) compared with the untreated group (0.15 ± 0.03 mM), which resulted in greater myocardial free fatty acid oxidation. In contrast, the group receiving {beta}-hydroxybutyrate in addition to fat emulsion had elevated {beta}-hydroxybutyrate concentration (0.87 ± 0.11 vs. 0.04 ± 0.01 mM), but suppressed fatty acid oxidation (0.053 ± 0.013 µmol·g–1·min–1) (P < 0.05) compared with the fat emulsion group (0.116 ± 0.029 µmol·g–1·min–1). There were no differences among the three groups in the tissue content for malonyl-CoA, acetyl-CoA, or free CoA or the activity of acetyl-CoA carboxylase; thus the inhibition of fatty acid oxidation by elevated {beta}-hydroxybutyrate did not appear to be due to malonyl-CoA inhibition of carnitine palmitoyl transferase-I or to an increase in the acetyl-CoA-to-free CoA ratio. In conclusion, fatty acid uptake and oxidation is blocked by an infusion of {beta}-hydroxybutyrate; this effect was not due to elevated myocardial malonyl-CoA content.

cardiac; heart; lactate; metabolism


Address for reprint requests and other correspondence: W. C. Stanley, Dept. of Physiology and Biophysics, School of Medicine, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-4970 (E-mail: WCS4{at}po.cwru.edu).




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