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Am J Physiol Endocrinol Metab 281: E983-E990, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 5, E983-E990, November 2001

Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a 13C isotopomer analysis

Julia J. Krueger1,4, Xue-Han Ning1,3, Barisa M. Argo1, Outi Hyyti1, and Michael A. Portman1,3

1 Division of Cardiology, Department of Pediatrics, University of Washington, School of Medicine, Seattle 98195; 3 Children's Hospital and Regional Medical Center, Seattle, Washington 98105; and 4 University of Hamburg School of Medicine, 20246 Hamburg, Germany.

Triiodothyronine (T3) exerts direct action on myocardial oxygen consumption (MVO2), although its immediate effects on substrate metabolism have not been elucidated. The hypothesis, that T3 regulates substrate selection and flux, was tested in isovolumic rat hearts under four conditions: control, T3 (10 nM), epinephrine (Epi), and T3 and Epi (TE). Hearts were perfused with [1,3-13C]acetoacetic acid (AA, 0.17 mM), L-[3-13C]lactic acid (LAC, 1.2 mM), U-13C-labeled long-chain free fatty acids (FFA, 0.35 mM), and unlabeled D-glucose (5.5 mM) for 30 min. Fractional acetyl-CoA contribution to the tricarboxylic acid cycle (Fc) per substrate was determined using 13C NMR and isotopomer analysis. Oxidative fluxes were calculated using Fc, the respiratory quotient, and MVO2. T3 increased (P < 0.05) FcFFA, decreased FcLAC, and increased absolute FFA oxidation from 0.58 ± 0.03 to 0.68 ± 0.03 µmol · min-1 · g dry wt-1 (P < 0.05). Epi decreased FcFFA and FcAA, although FFA flux increased from 0.58 ± 0.03 to 0.75 ± 0.09 µmol · min-1 · g dry wt-1. T3 moderated the change in FcFFA induced by Epi. In summary, T3 exerts direct action on substrate pathways and enhances FFA selection and oxidation, although the Epi effect dominates at a high work state.

metabolism; mitochondria; free fatty acids; nuclear magnetic resonance


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