Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart

Abstract

The hormonal regulation and enzymatic basis of endogenous lipolysis in heart are not yet completely elucidated. The lysosomal fraction from rat heart appeared to be markedly enriched in triglycerides and a significant reduction in triglycerides in this fraction was found after prolonged perfusion or stimulation of lipolysis with glucagon. The enhanced rate of lipolysis, measured as glycerol release from the isolated perfused rat heart, was abolished 10-15 min after continuous glucagon administration. Omission of glucagon for another 60 min restored the ability of glucagon to stimulate lipolysis, indicating the limited availability of endogenous triglycerides and the presence of a transfer-system for triglycerides from a non-metabolically active pool to a metabolically active pool. The enhanced lipolysis induced by low-flow ischemia was found to be inhibited by the lysosomotropic agent methylamine (5 mM). Methylamine-perfusion during low-flow ischemia was accompanied by an increased recovery of myocardial triglycerides in the lysosomal fraction. The possible role of lysosome-like particles in myocardial triglyceride homeostasis was further investigated by studying the kinetics of uptake and degradation of labeled triglycerides by membrane-particles recovered in the subcellular fraction enriched with lysosomal marker enzymes. It appeared that isolated lysosomal membranes take up added triglycerides at an average rate of 30 nmoles/min/g protein. The bulk of these triglycerides taken up is stored whereas 20% is degraded to diglycerides and free fatty acids. More than 90% of the free fatty acids formed were released from the lysosomes into the supernatant. The uptake and degradation of triglyceride-filled liposomes by isolated myocardial lysosomes was inhibited during incubation with methylamine (5 mM). On the other hand, a lowering of pH during in vitro incubation increased the rate of uptake and degradation of added triglycerides by isolated lysosomes. These results indicate that lysosomes or lysosome-like particles are involved in the enhanced lipolysis during myocardial ischemia.

Overexpression of Vascular Endothelial Growth Factor-B in Mouse Heart Alters Cardiac Lipid Metabolism and Induces Myocardial Hypertrophy

“…This process is linked both to cardioprotection and lipolysis. A major portion of myocardial intracellular triacylglycerol hydrolysis is lysosomal32, and lysosomes are involved in autophagosome formation31. Moreover, increasing the autophagic capacity of cardiomyocytes decreased apoptosis induction upon ischemia-reperfusion33.…”

Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure

“…It has also been reported that ACE inhibition improves 123 I-BMIPP uptake in patients with acute myocardial infarction who have received successful coronary revascularization [18]. It has been reported that triglyceride turnover is enhanced in the failing heart [19,20]. As 123 I-BMIPP is partly trapped in the triglyceride fraction in the cardiomyocyte [21], enhanced triglyceride turnover may increase 123 I-BMIPP washout from the myocardium.…”

Dynamic 123I‐BMIPP single‐photon emission computed tomography in patients with congestive heart failure: Effect of angiotensin ii type‐1 receptor blockade

“…19 Second, triglyceride turnover is enhanced in the failing heart. 20,21 Since BMIPP is partly trapped into triglyceride fraction in the cardiomyocyte, 12 enhanced triglyceride turnover may increase BMIPP washout from the myocardium. Third, the depressed level of fatty acid-binding protein may cause decreased BMIPP uptake and enhanced BMIPP washout in the early phase soon after tracer injection.…”