Enhanced lipolysis of myocardial triglycerides during low-flow ischemia and anoxia in the isolated rat heart

Abstract

We studied lipolysis in the isolated rat heart, measured as glycerol release during anoxia, low-flow ischemia and subsequent reperfusion. It was found that the rate of lipolysis was enhanced during ischemia/anoxia while the lipase activities in tissue extracts involved in the myocardial lipolysis and the amount of triglycerides were not affected. This indicates the dominant occurrence of a lipolysis-reesterification principle in ischemic and anoxic tissue. A common observation of ischemia/anoxia is an increase in the tissue NADH/NAD+ ratio. Therefore we investigated the effect of lactate and malate, both of which enhance the tissue redox state on myocardial lipolysis. Perfusion in the presence of lactate (10 mM) and malate (10 mM) both stimulated myocardial lipolysis by about five times. This suggests that the rate of reesterification of product fatty acids to triglycerides, which is determined by the NADH/NAD+ ratio, because of the increased formation of glycerol 3-phosphate from dihydroxy acetone phosphate, plays an important role in the regulation of lipolysis. The existence of triglyceride-fatty acid-triglyceride cycle is discussed.

Myocardial fatty acid oxidation during ischemia and reperfusion

“…Indeed, net accumulation of triacylglycerols during ischemia has been observed in several studies [13,26,27], but is not a constant finding [28]. There is evidence that not only synthesis, but also hydrolysis of triacylglycerols is accelerated during ischemia [15,29,30]. Because thioesterification of fatty acids with Coenzyme A requires ATP, hydrolysis and subsequent resynthesis of triacylglycerols results in an energy-consuming metabolic cycle [29,30].…”

“…There is evidence that not only synthesis, but also hydrolysis of triacylglycerols is accelerated during ischemia [15,29,30]. Because thioesterification of fatty acids with Coenzyme A requires ATP, hydrolysis and subsequent resynthesis of triacylglycerols results in an energy-consuming metabolic cycle [29,30]. On the basis of observed rates of glycerol release [29,30] in isolated rat hearts subjected to low-flow ischemia, the rate of ATP utilization in this metabolic cycle can be estimated to be of the order of 0.10-0.25/zmol ATP-min-l.g wet weight -a [29,30].…”

Mechanical and Metabolic Characterization of Ischemic Contracture in the Neonatal Pig Heart

“…Because P-oxidation is impaired during ischemia, re-esterification of the FFA back to triglycerides becomes the primary means of removing the potentially harmful intracellular lipids. This cycle, l~owever, is an ATPconsuming process (16,42,43). Based on the glycerol release, and assuming that glycerol 3-phosphate comes from glycogenolysis, we estimate that ATP utilization from the breakdown of triglycerides and complete reesterification of the FFA would constitute only =6% of the ATP production from glucose.…”

“…Thus, a substantial portion of the myocardial triglyceride pool in our piglet hearts may have undergone lipolysis during the low-flow state. The mechanism underlying an enhanced rate of lipolysis during ischemia is incompletely understood, although Schoonderwoerd et al (16) have provided evidence to suggest that triglyceride breakdown is stimulated by an elevated NADH/NADt ratio. Because P-oxidation is impaired during ischemia, re-esterification of the FFA back to triglycerides becomes the primary means of removing the potentially harmful intracellular lipids.…”

“…Inasmuch as supplementary fatty acids were not included in the perfusate, endogenous myocardial triglycerides became the primary source of lipids available for metabolism. Triglycerides can be hydrolized to glycerol and FFA, and heart tissue is deficient in glycerol kinase (16). Thus, glycerol release can be used as an indirect marker for hydrolysis of triglycerides.…”