低HDL血症患者のHDL代謝における肝性トリグリセリドリパーゼの役割

Abstract

It has been indicated that lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) play a role not only in the metabolism of triglyceride rich lipoproteins but also in HDL metabolism. The purpose of the present study was to investigate the role of LPL and H-TGL in the metabolism of HDL-subfractions, HDL2 and HDL3 in the subjects with hypo-high density lipoproteinemia. Clinical diagnosis of the 29 patients with hypohigh density lipoproteinemia studied in the present study were postapoplexy in the steady state, coronary heart disease and hypertension etc. Furthermore, seventeen hypo-high density lipoproteinemia with diabetes mellitus, 19 subjects with normal levels of HDL-cholesterol (C) and 8 diabetics with normal levels of HDL-C were studied. Hypo-high density lipoproteinemia was defined by (HDL2+HDL3)-cholesterol less than 40mg/100ml. Plasma lipoproteins were fractionated by sequential ultracentrifugation at densities 1.063 and 1.110g/ml to obtain VLDL+LDL(d<1.063g/ml), HDL2(1.063<d<1.110g/ml) and HDL3 (d>1.110g/ml). Concentrations of cholesterol, triglyceride and phospholipid in plasma and each lipoprotein fraction were measured. Activities of LPL and H-TGL in postheparin plasma obtained 10min after injection of heparin, 10U/Kg body weight, were assayed utilizing the substrate containing [14C] triolein. Separate assay of LPL and H-TGL activities were performed by inhibition of LPL activity by 1M NaCl. Cholesterol concentrations in HDL2 and HDL3 from hypohigh density lipoproteinemia were significantly lower than those from the patients with normal levels of HDL-C. Decrease of HDL2-cholesterol was more remarkable than that of HDL3-cholesterol. Therefore, HDL2-Ch/HDL3-Ch ratio was significantly lower in hypo-high density lipoproteinemia than in the patients with normal levels of HDL-Ch. As far as phospholipid is concerned, the same tendency was observed as cholesterol. There was no significant difference in triglyceride concentration in HDL2 and HDL3 between hypo- and normo-high density lipoproteinemia. LPL activity was significantly lower in hypo-high density lipoproteinemia without diabetes mellitus than in normo-high density lipoproteinemia. There were no significant differences in H-TGL activities among 4 groups. In hypo-high density lipoproteinemia, significantly negative correlations were observed between H-TGL activities and concentrations of cholesterol and phospholipid in HDL2. Significantly positive correlations were observed between LPL activities and concentrations of triglyceride and phospholipid in HDL2. However, there were no significant correlations among LPL activity, H-TGL activity and lipids concentrations in HDL3. These correlations were much more obvious in diabetics with hypo-high density lipoproteinemia. The data presented indicate the important role of LPL and H-TGL in the metabolism of HDL2 and HDL3 in the subjects with hypo-high density lipoproteinemia.