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

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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.

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Acknowledgments

This work was supported in part by National High Technology R&D Program of China (863 Program No. 2006AA02Z119), National Natural Science Foundation of the People’s Republic of China (No. 30821001), Major National Basic Research Program of the People’s Republic of China (No. G2006CD503801) and Beijing Natural Science Foundation (No. 5101004) to G. Liu.

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China

    Yinyuan Ding, Yuhui Wang & George Liu

  2. Laboratory Animal Center, Xi’an Jiaotong University, Xi’an, 710061, China

    Hong Zhu & Enqi Liu

  3. Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan

    Jianglin Fan

  4. Department of Pathology Section on Lipid Sciences, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157-1040, USA

    Liqing Yu

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  1. Yinyuan Ding
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  2. Yuhui Wang
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  3. Hong Zhu
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  4. Jianglin Fan
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  5. Liqing Yu
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  6. George Liu
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  7. Enqi Liu
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Correspondence to George Liu or Enqi Liu.

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Ding, Y., Wang, Y., Zhu, H. et al. Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII. Transgenic Res 20, 867–875 (2011). https://doi.org/10.1007/s11248-010-9467-5

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  • DOI: https://doi.org/10.1007/s11248-010-9467-5

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