Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a (13)C isotopomer analysis.
Triiodothyronine (T(3)) exerts direct action on myocardial oxygen consumption (MVO(2)), although its immediate effects on substrate metabolism have not been elucidated. The hypothesis, that T(3) regulates substrate selection and flux, was tested in isovolumic rat hearts under four conditions: control, T(3) (10 nM), epinephrine (Epi), and T(3) and Epi (TE). Hearts were perfused with [1,3-(13)C]acetoacetic acid (AA, 0.17 mM), L-[3-(13)C]lactic acid (LAC, 1.2 mM), U-(13)C-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 (13)C NMR and isotopomer analysis. Oxidative fluxes were calculated using Fc, the respiratory quotient, and MVO(2). T(3) increased (P < 0.05) Fc(FFA), decreased Fc(LAC), and increased absolute FFA oxidation from 0.58 +/- 0.03 to 0.68 +/- 0.03 micromol. min(-1). g dry wt(-1) (P < 0.05). Epi decreased Fc(FFA) and Fc(AA), although FFA flux increased from 0.58 +/- 0.03 to 0.75 +/- 0.09 micromol. min(-1). g dry wt(-1). T(3) moderated the change in Fc(FFA) induced by Epi. In summary, T(3) exerts direct action on substrate pathways and enhances FFA selection and oxidation, although the Epi effect dominates at a high work state.
Krueger
J J
JJ
Division of Cardiology, Department of Pediatrics, University of Washington, School of Medicine, Seattle 98195, USA.
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D000090:Acetoacetates / Q000008:administration & dosage / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D004837:Epinephrine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D000090:Acetoacetates; D005230:Fatty Acids, Nonesterified; D014284:Triiodothyronine; D019344:Lactic Acid; C016635:acetoacetic acid; D000105:Acetyl Coenzyme A; D005947:Glucose; D004837:Epinephrine