Influence of lipoprotein lipase and hepatic lipase on the transformation of VLDL and HDL during lipolysis of VLDL Original Research Article

In order to study the relative effects of lipolytic enzymes on the removal of lipids and apolipoproteins, in particular apolipoprotein (apo) E and cholesteryl ester, from human very low density lipoprotein (VLDL) during its conversion to product lipoproteins, the action of lipoprotein lipase (LPL) and the combined action of lipoprotein lipase and hepatic lipase (HL) were studied in the presence of physiological proportions of high density lipoprotein (HDL) (10 mg protein). VLDL (2 mg protein) and albumin in an amount sufficient for the binding of all released fatty acids. The HDL used in the incubation was free of apo E in order to facilitate assessment of apo E transfer from VLDL to HDL. The redistribution of lipid and apolipoprotein mass and the movement of labeled cholesteryl ester from VLDL to other lipoprotein fractions was assessed by density gradient ultracentrifugation. Following 90%–95% lipolysis of VLDL triglycerides by rat heart LPL in 2 h, there was an almost complete transfer of apo C-II and apo C-III to HDL but only 20% of VLDL apo E was transferred to HDL. There was significant augmentation of HDL unesterified cholesterol and phospholipid mass during LPL action despite a substantial overall phospholipid hydrolysis (30%). The transfer of cholesteryl ester mass to HDL was variable (0%–13%) with a mean transfer of 7% of VLDL cholesteryl ester. Transfer of labeled VLDL cholesteryl ester to HDL was 3%–6%. A considerable amount of the VLDL lipid mass appeared in the light fraction of the low density lipoprotein (LDL) region, but a substantial amount remained in the VLDL/intermediate density lipoprotein (IDL) region. The post-lipolysis particles that were isolated in the VLDL-LDL density range were larger than LDL and contained a high ratio of surface lipids relative to core lipids as compared to plasma LDL. The inclusion of human HL with LPL did not alter the redistribution of apolipoproteins or lipids from VLDL to LDL or to HDL. The major effect of HL, relative to that observed with LPL alone, was a marked hydrolysis of HDL triglycerides (68%). Despite the combined action of LPL and HL on VLDL in the presence of HDL and over 90% lipolysis of triglycerides, a major portion of residual VLDL mass remained in fractions lighter than normal LDL density and retained apo E. It is concluded that lipoprotein lipase or LPL in combination with HL are ineffective in bringing about the complete conversion of plasma VLDL to LDL. Lipoprotein lipase was effective in substantially augmenting the HDL mass including cholesteryl ester mass while the major effect of HL was the selective hydrolysis of HDL triglycerides.