Competition between lactate and fatty acids as sources of ATP in the isolated working rat heart

Abstract

Fatty acid oxidation is generally considered the major source of energy in the heart, although lactate oxidation can be a major contributor to ATP production, depending on the concentration and availability of other competing substrates. In this study, isolated working rat hearts were used to directly determine the relationship between lactate and fatty acid oxidation to overall ATP production from exogenous sources. A range of lactate from 0.5 to 8.0 mM lactate was added to hearts perfused with buffer containing 5.5 mM glucose, and either 0.4 or 1.2 mM palmitate over a 100 min period. Rates of glycolysis, glucose oxidation, lactate oxidation, and palmitate oxidation were determined. In the presence of 0.5 mM lactate and 0.4 mM palmitate, lactate oxidation provided 17% of the ATP production and palmitate oxidation provided 68%, with the remainder coming from glucose oxidation and glycolysis. In the presence of 0.4 mM palmitate, an increase in lactate from 0.5 to 8.0 mM increased the steady state rates of lactate oxidation from 1239+/-236 to 5247+/-940 nmol/min/g dry weight, respectively. The contribution of lactate oxidation to total ATP production increased to 37%, with palmitate oxidation now contributing only 52% of the total ATP produced. At 8.0 mM lactate and 1.2 mM palmitate, lactate oxidation contributed 13% of the total ATP production, while palmitate oxidation contributed 81%. This data demonstrates that under near physiological conditions of lactate (0.5 mM) and fatty acids (0.4 mM), the preferred energy substrate of the heart remains to be fatty acids, and that only at high levels of lactate, such as can be observed during exercise or severe stress, does lactate oxidation become a significant source of ATP production.