Heparin-induced lipolysis in hypertriglyceridemic subjects results in the formation of atypical HDL particles.

Abstract

This study reports on the characterization of high density lipoprotein (HDL) in normotriglyceridemic and hypertriglyceridemic (HTG) subjects, after a fat meal and heparin-induced release of lipases. Samples for detailed analysis of HDL by density gradient ultracentrifugation and nondenaturing gradient gel electrophoresis were collected at 0 h and 5 h after the meal and 15 min after the administration of heparin. The normotriglyceridemic subjects were subdivided into two groups: those who remained normotriglyceridemic 5 h after the meal (NTG) or those who were hypertriglyceridemic at this time point (NTG-HTG). At the outset of the study, mean triglyceride levels were significantly higher (P < 0.001) and HDL cholesterol levels lower (P < 0.02) in the HTG group. The HDL particles in this group were enriched with triglyceride (P < 0.001). Serum triglyceride levels rose in all three groups after the fat meal and this was associated with further triglyceride enrichment of the HDL particles. In all groups, rapid lipolysis induced by heparin caused a significant decrease in plasma triglycerides and increase in free fatty acid levels, these changes being greatest in the HTG group. HDL density profiles of the study groups prior to the administration of heparin demonstrated two distinct peaks at density 1.09 g/ml (HDL2) and 1.13 g/ml (HDL3). However, after the administration of heparin to the HTG group, only a single peak in the HDL profile was evident that was located at the density region corresponding to HDL2 (1.09 g/ml). Upon gradient gel electrophoresis of this peak, there was an increased number (P < 0.005 vs. NTG) of small particles (< 4.37 nm) whose size was similar to the size range normally associated with HDL3b and HDL3c. Similar changes in HDL density and size after the administration of heparin were observed in the NTG-HTG group who were also hypertriglyceridemic postprandially. By contrast, the density gradient profiles and sizes of the HDL particles did not change after the administration of heparin to NTG subjects. Thus, the activation of lipolysis in HTG subjects leads to the generation of atypical HDL particles that are small but of reduced density. Rapid clearance of such particles could account for the inverse relationship between triglyceride and HDL cholesterol in this population subgroup.