Stimulation of Myocardial Neutral Triglyceride Lipase Activity by Adenosine-3':5'-monophosphate: Involvement of Glycogenolysis

Endogenous lipolysis can be influenced by various hormones. Hormonal stimulation of endogenous lipolysis in the Langendorff heart was diminished by inhibition of glycogenolysis. Therefore we studied the influence of glycogenolysis on the cAMP-dependent activation of the neutral triglyceride lipase activity using a 40,000 X g post mitochondrial supernatant fraction from rat heart homogenates. In the presence of cAMP and ATP neutral triglyceride lipase activity was stimulated by 40%. This stimulation could not be detected in supernatants from which glycogen was removed after incubation in the presence of amyloglucosidase. Addition of glycogen overcomes this loss of stimulation. The activation of neutral triglyceride lipase by cAMP and ATP was mimicked by glucose plus ATP as well as by glycerol-3-phosphate but not by glyceraldehyde-3-phosphate. Moreover, the cAMP stimulation of neutral triglyceride lipase activity was suppressed by low amounts of palmitoyl-CoA indicating product inhibition of lipase activity. These results indicate that the level of intracellular precursors of fatty acid re-esterification, by determining the removal rate of product fatty acids, may be the major determinant of the stimulation of lipolysis by cAMP.