ACUTE EFFECTS OF ADRENALINE ON HEPATIC LIPASE SECRETION BY RAT HEPATOCYTES

Catecholamines are responsible for the daily changes in hepatic lipase (HL) expression associated with feeding and fasting. We have studied the mechanism by which adrenaline decreases HL secretion in suspension s of freshly isolated rat hepatocytes. Adrenaline acutely inhibited HL activity through activation of the alpha(1)-adrenergic pathway, The c ells had significantly less HL activity in the presence of adrenaline versus cycloheximide, where protein de novo synthesis is completely bl ocked. The specific enzyme activity of secreted HL was not affected, I ntracellular HL activity was decreased by adrenaline treatment, Pulse- labeling with [S-35]methionine showed that de novo synthesis of the 53 -kd endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive HL protein was unaffected by adrenaline. During subsequent chase of the control c ells, the 53-kd form was converted to a 58-kd Endo H-resistant HL prot ein, which was rapidly secreted into the medium, In the presence of ad renaline, formation of the 58-kd protein was markedly reduced, whereas the 53-kd protein disappeared at a rate similar to the rate in contro ls. This suggests that part of the HL protein was degraded, In contras t to adrenaline, inhibition of HL secretion by colchicine was accompan ied by an intracellular accumulation of HL activity and of the 58-kd p rotein, We conclude that adrenaline inhibits HL secretion posttranslat ionally by retarding the maturation of the 53-kd HL precursor to an ac tive 58-kd protein, possibly by stimulating degradation of newly synth esized HL protein. Copyright (C) 1997 by W.B. Saunders Company