ALTERATION OF LIPID PROFILES IN PLASMA OF TRANSGENIC MICE EXPRESSING HUMAN LIPOPROTEIN-LIPASE

Lipoprotein lipase (LPL) is a key enzyme required for the hydrolysis o f triglyceride-rich particles. To assess the effects of increased plas ma LPL on lipoprotein levels, transgenic mice expressing human LPL (hL PL) were produced. Abundant hLPL transcripts were detected in RNA from different tissues of transgenic mice which resulted in an increase in post-heparin plasma LPL activity of approximately 154%. On rodent cho w (p = 0.01) and after a 16-h fast (p = 0.001), plasma triglycerides i n transgenic mice were decreased by approximately 50% as compared to l ittermate controls. Gel filtration chromatography showed a 2-3-fold de crease in very low density lipoprotein triglycerides and cholesterol e nrichment of low density lipoprotein. Transgenic mice maintained on a high carbohydrate diet exhibited a 78% (p = 0.03) lowering of low dens ity lipoprotein and very low density lipoprotein cholesterol levels, i n addition to a 68% (p = 0.01) lowering of total to high density lipop rotein cholesterol (TC/HDL-C) ratios compared to controls. The distrib ution of apoA-I and A-II were similar in the transgenics and their non -transgenic littermates, while the apoE distribution was mildly altere d in the plasma from the transgenic mice. These data demonstrate that moderate increases in total LPL activity are associated with significa nt changes in lipoprotein levels and altered composition of lipoprotei n particles.