Hormonal regulation of myocardial lipolysis.

Abstract

Although it has been documented that hormones promote lipolysis in the heart, an enzyme mediating this event has not been identified. We have found that perfusion of the rat heart with epinephrine, 3-isobutyl-1-methylxanthine, or dibutyryl (Bt2) cyclic AMP produced a biphasic effect on the activity of an enzyme having the properties of the intracellular fraction of lipoprotein lipase, i.e., stability in acetone:ether, pH optimum of 8.1, serum requirement, and sensitivity to heparin, NaCl, and protamine sulfate. We have termed this enzyme type L hormone-sensitive lipase (HSL). Perfusion with high concentrations of agent stimulate type L HSL activity, while perfusion with relatively low concentrations of agent inhibit enzyme activity. This inhibition is not observed if enzyme is extracted in organic solvent. The activity of type L HSL has a high negative (r greater than -0.93) relationship with the amount of triglyceride in the heart. Early attempts to purify this enzyme from control and epinephrine-stimulated hearts suggest that the enzyme can be obtained in two forms (control and activated). Although the data suggest that the mechanism of control of this enzyme is complex, it seems that the activity is controlled, in part, through cyclic AMP and protein kinase.