Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase.
Lipoprotein lipase (LPL) is a key enzyme required for the hydrolysis of triglyceride-rich particles. To assess the effects of increased plasma LPL on lipoprotein levels, transgenic mice expressing human LPL (hLPL) 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 chow (p = 0.01) and after a 16-h fast (p = 0.001), plasma triglycerides in transgenic mice were decreased by approximately 50% as compared to littermate controls. Gel filtration chromatography showed a 2-3-fold decrease in very low density lipoprotein triglycerides and cholesterol enrichment of low density lipoprotein. Transgenic mice maintained on a high carbohydrate diet exhibited a 78% (p = 0.03) lowering of low density lipoprotein and very low density lipoprotein cholesterol levels, in addition to a 68% (p = 0.01) lowering of total to high density lipoprotein cholesterol (TC/HDL-C) ratios compared to controls. The distribution of apoA-I and A-II were similar in the transgenics and their non-transgenic littermates, while the apoE distribution was mildly altered in the plasma from the transgenic mice. These data demonstrate that moderate increases in total LPL activity are associated with significant changes in lipoprotein levels and altered composition of lipoprotein particles.
Liu
M S
MS
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Jirik
F R
FR
LeBoeuf
R C
RC
Henderson
H
H
Castellani
L W
LW
Lusis
A J
AJ
Ma
Y
Y
Forsythe
I J
IJ
Zhang
H
H
Kirk
E
E
D000818:Animals; D015152:Blotting, Northern; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003587:Cytomegalovirus; D005260:Female; D017781:Genes, Immediate-Early; D006801:Humans; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase