Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

The effects of long-chain (LC) fatty acids on rate of heat production (heat rate) and mitochondrial membrane potential (Deltapsi) of intact guinea pig cardiac muscle were investigated at 37degreesC. Heat rate of ventricular trabeculae was measured with microcalorimetry, and Deltapsi was monitored in isolated ventricular myocytes with either JC-1 or tetramethylrhodamine ethyl ester (TMRE). Methyl-beta-cyclodextrin was used as fatty acid carrier. Application of 400 muM oleate or linoleate increased resting heat rate by similar to30% and similar to25%, respectively. When LC fatty acid was supplied as sole metabolic substrate, resting heat rate was decreased by 3-mercaptopropionic acid. In TMRE-loaded myocytes, neither 40-80 muM oleate nor 40 muM linoleate affected Deltapsi. At a higher concentration (400 muM) both oleate and linoleate increased TMRE fluorescence by similar to20% of maximum, obtained using 2,4-dinitrophenol (100 muM), indicating a depolarization of the inner mitochondrial membrane. We conclude that LC fatty acids, at sufficiently high concentration, increase heat rate and decrease Deltapsi in intact cardiac muscle, consistent with a protonophoric uncoupling action. These effects may contribute to the high metabolic rate after reperfusion of postischemic myocardium.