Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase

Ming Sun Liu, Frank R. Jirik, Renee C. LeBoeuf, Howard Henderson, Lawrence W. Castellani, Aidons J. Lusis, Yuanhong Ma, Ian J. Forsythe, Hanfang Zhang, Elizabeth Kirk, John D. Brunzell, Michael R. Hayden

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)11417-11424
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number15
StatePublished - Apr 15 1994

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Lipoprotein Lipase
Transgenic Mice
Lipoproteins
Lipids
Plasmas
VLDL Cholesterol
Triglycerides
LDL Lipoproteins
Apolipoprotein A-I
Apolipoproteins E
Nutrition
Chromatography
HDL Cholesterol
Heparin
Hydrolysis
Gels
Carbohydrates
Gel Chromatography
RNA
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Liu, M. S., Jirik, F. R., LeBoeuf, R. C., Henderson, H., Castellani, L. W., Lusis, A. J., ... Hayden, M. R. (1994). Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. Journal of Biological Chemistry, 269(15), 11417-11424.

Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. / Liu, Ming Sun; Jirik, Frank R.; LeBoeuf, Renee C.; Henderson, Howard; Castellani, Lawrence W.; Lusis, Aidons J.; Ma, Yuanhong; Forsythe, Ian J.; Zhang, Hanfang; Kirk, Elizabeth; Brunzell, John D.; Hayden, Michael R.

In: Journal of Biological Chemistry, Vol. 269, No. 15, 15.04.1994, p. 11417-11424.

Research output: Contribution to journalArticle

Liu, MS, Jirik, FR, LeBoeuf, RC, Henderson, H, Castellani, LW, Lusis, AJ, Ma, Y, Forsythe, IJ, Zhang, H, Kirk, E, Brunzell, JD & Hayden, MR 1994, 'Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase', Journal of Biological Chemistry, vol. 269, no. 15, pp. 11417-11424.
Liu MS, Jirik FR, LeBoeuf RC, Henderson H, Castellani LW, Lusis AJ et al. Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. Journal of Biological Chemistry. 1994 Apr 15;269(15):11417-11424.
Liu, Ming Sun ; Jirik, Frank R. ; LeBoeuf, Renee C. ; Henderson, Howard ; Castellani, Lawrence W. ; Lusis, Aidons J. ; Ma, Yuanhong ; Forsythe, Ian J. ; Zhang, Hanfang ; Kirk, Elizabeth ; Brunzell, John D. ; Hayden, Michael R. / Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 15. pp. 11417-11424.
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abstract = "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.",
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