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.