Impaired Myocardial Fatty Acid Oxidation and Reduced Protein Expression of Retinoid X Receptor-α in Pacing-Induced Heart Failure

Abstract

Background— The nuclear receptors peroxisome proliferator-activated receptor-α (PPARα) and retinoid X receptor α (RXRα) stimulate the expression of key enzymes of free fatty acid (FFA) oxidation. We tested the hypothesis that the altered metabolic phenotype of the failing heart involves changes in the protein expression of PPARα and RXRα. Methods and Results— Cardiac substrate uptake and oxidation were measured in 8 conscious, chronically instrumented dogs with decompensated pacing-induced heart failure and in 8 normal dogs by infusing 3 isotopically labeled substrates: 3H-oleate, 14C-glucose, and 13C-lactate. Although myocardial O2 consumption was not different between the 2 groups, the rate of oxidation of FFA was lower (2.8±0.6 versus 4.7±0.3 μmol · min−1 · 100g−1) and of glucose was higher (4.6±1.0 versus 1.8±0.5 μmol · min−1 · 100g−1) in failing compared with normal hearts (P<0.05). The rates of lactate uptake and lactate output were not significantly different between the 2 groups. In left ventricul...