Relation between lipolysis and glycolysis during ischemia in the isolated rat heart

Abstract

The relation between lipolysis and glycolysis during ischemia was investigated in isolated perfused rat hearts. In hearts perfused with 11 mM glucose, ischemia caused a marked increase of glycerol release from 10 to 33 nmol/g wt weight/min. Substrate-free perfusion induced an initial stimulation of glycerol release, but lipolysis was subsequently reduced to values comparable to normoxic conditions. Neither did perfusion in the presence of acetate (10 mM) and beta-hydroxybutyrate (10 mM) stimulate lipolysis. Inhibition of glycolysis by pyruvate prevented the increase of glycerol release during ischemia. These data suggest a tight link between glycolysis and lipolysis during ischemia which is probably mediated by the availability of glycolytically produced glycerol-3-phosphate for reesterification. In the absence of glycerol-3-phosphate, the lipolysis is regulated by product inhibition. As a consequence, the tissue triglyceride levels after perfusion remained fairly constant in all groups of hearts. The calculated energy loss by the reesterification cycle during ischemia was found to be approximately 2.5% of the total energy production. These data are inconsistent with the assumption that this energy loss contributes significantly to the negative energetic balance of the heart during ischemia. Removal of fatty acids by reesterification may constitute a protective mechanism in order to prevent excessive intracellular accumulation of fatty acids and derivative esters during ischemia.

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].…”

Simultaneous measurement of both lipid and lactate in isolated rat hearts by 1H NMR spectroscopy

“…The rate of glycolysis has been shown to be a primary regulatory factor in triacylglycerol lipolysis (25), with increased glycolysis leading to decreased lipolysis, measured via glycerol release. This is not consistent with our data, in which decreased glycolysis (during IAA inhibition) leads to increased lipolysis.…”

“…23 g; n = 17) were anesthetized intraperitoneally with sodium pentobarbital. The hearts were removed, arrested in ice-cold buffer, and retrograde perfused at a constant pressure of 100 mmHg (8) with modified (phosphate-free) KrebsHenseleit buffer containing (mmol/liter) NaCl (118), KC1 (4.7), CaC1, (1.5), MgSO, (2.4), Na,H,EDTA (0.5), NaHCO, (25), and glucose (11) or sodium acetate (5). For some experiments, 0.15 mMiodoacetate (IAA) was added to the acetate buffer.…”

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.…”