Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII

Yinyuan Ding, Yuhui Wang, Hong Zhu, Jianglin Fan, Liqing Yu, George Liu, Enqi Liu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.

Original languageEnglish (US)
Pages (from-to)867-875
Number of pages9
JournalTransgenic Research
Volume20
Issue number4
DOIs
StatePublished - Aug 1 2011

Fingerprint

Apolipoprotein C-III
hypertriglyceridemia
apolipoproteins
Hypertriglyceridemia
rabbits
Fats
genetically modified organisms
Rabbits
lipids
lipoprotein lipase
Lipoprotein Lipase
triacylglycerols
Triglycerides
chylomicrons
very low density lipoprotein
Chylomicrons
heparin
hyperlipidemia
VLDL Lipoproteins
high density lipoprotein cholesterol

Keywords

  • Apolipoprotein CIII
  • Hypertriglyceridemia
  • Transgenic rabbit

ASJC Scopus subject areas

  • Biotechnology
  • Animal Science and Zoology
  • Genetics
  • Agronomy and Crop Science

Cite this

Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII. / Ding, Yinyuan; Wang, Yuhui; Zhu, Hong; Fan, Jianglin; Yu, Liqing; Liu, George; Liu, Enqi.

In: Transgenic Research, Vol. 20, No. 4, 01.08.2011, p. 867-875.

Research output: Contribution to journalArticle

Ding, Yinyuan ; Wang, Yuhui ; Zhu, Hong ; Fan, Jianglin ; Yu, Liqing ; Liu, George ; Liu, Enqi. / Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII. In: Transgenic Research. 2011 ; Vol. 20, No. 4. pp. 867-875.
@article{f0dd90687baa457fa865d11915979502,
title = "Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII",
abstract = "Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.",
keywords = "Apolipoprotein CIII, Hypertriglyceridemia, Transgenic rabbit",
author = "Yinyuan Ding and Yuhui Wang and Hong Zhu and Jianglin Fan and Liqing Yu and George Liu and Enqi Liu",
year = "2011",
month = "8",
day = "1",
doi = "10.1007/s11248-010-9467-5",
language = "English (US)",
volume = "20",
pages = "867--875",
journal = "Transgenic Research",
issn = "0962-8819",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII

AU - Ding, Yinyuan

AU - Wang, Yuhui

AU - Zhu, Hong

AU - Fan, Jianglin

AU - Yu, Liqing

AU - Liu, George

AU - Liu, Enqi

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.

AB - Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.

KW - Apolipoprotein CIII

KW - Hypertriglyceridemia

KW - Transgenic rabbit

UR - http://www.scopus.com/inward/record.url?scp=79960442664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960442664&partnerID=8YFLogxK

U2 - 10.1007/s11248-010-9467-5

DO - 10.1007/s11248-010-9467-5

M3 - Article

C2 - 21120692

AN - SCOPUS:79960442664

VL - 20

SP - 867

EP - 875

JO - Transgenic Research

JF - Transgenic Research

SN - 0962-8819

IS - 4

ER -