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Overexpression of NPC1L1 in the livers of transgenic Bama miniature pigs accelerates lipid peroxidation

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Abstract

Although Niemann-Pick C1-Like 1 (NPC1L1) plays a key role in intestinal cholesterol absorption, regulating cholesterol metabolism and maintaining cholesterol metabolic homeostasis, the molecular mechanism of NPC1L1 in lipid-metabolism disorders leading to liver disease remains largely unknown. Previous studies have shown that NPC1L1 is related with the development of fatty liver. Therefore, we hypothesized that NPC1L1 plays an important role in lipid-metabolism disorders and liver disease by affecting the transcription of certain genes involved in lipid synthesis. To further elucidate the function of NPC1L1, especially in the liver, we used somatic-cell nuclear transfer to establish transgenic pigs that expressed human NPC1L1 in their livers. We investigated superoxide dismutase activities and the levels of free fatty acids and malondialdehyde, a biomarker of lipid peroxidation. Superoxide dismutase activities significantly decreased, and free fatty acid and malondialdehyde levels significantly increased in the NPC1L1 transgenic pigs, indicating that the overexpression of NPC1L1 in the liver resulted in severe lipid peroxidation. Our findings suggest that NPC1L1 plays an important role in lipid-metabolism disorders and liver disease.

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Acknowledgments

This work was supported by Grants from the National Science and Technology Supporting Plan of China (NO. 2011BAI15B02), Changjiang Scholars and Innovative Research Team in University (PCSIRT, No. IRT1248) and National High-tech R&D Program of China (863 Program) (2012AA020603). We gratefully thank Pr. H. Ouyang, D. Pang, H. Wei and L. Yu for their expert assistance and suggestions.

Conflict of interest

The authors declare that there are no conflicts of interest associated with the publication of this article.

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Authors and Affiliations

  1. Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Sciences, Jilin University, 5333 Xi An DaLu, Changchun, 130062, People’s Republic of China

    Chongli Xu, Xinping Duan, Xiaochun Tang, Mingjun Zhang, Daxin Pang & Hongsheng Ouyang

  2. College of Chemical Engineering and Biotechnology, Jilin Institute of Chemical Technology, 45 ChengDe Road, Jilin, 132022, People’s Republic of China

    Chongli Xu

  3. Department of Laboratory Animal Science, College of Basic Medicine, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Yu Liu & Hong Wei

  4. College of Animal Science, Jilin Agricultural University, Changchun, 130118, People’s Republic of China

    Yuchen Gong

  5. Department of Animal and Avian Sciences, University of Maryland, College Park, 20742, Maryland, USA

    Liqing Yu

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  1. Chongli Xu
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  2. Yu Liu
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  3. Yuchen Gong
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  4. Xinping Duan
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  5. Xiaochun Tang
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  8. Liqing Yu
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  9. Hong Wei
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  10. Hongsheng Ouyang
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Correspondence to Liqing Yu, Hong Wei or Hongsheng Ouyang.

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Chongli Xu and Yu Liu these authors have contributed equally to this paper.

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Xu, C., Liu, Y., Gong, Y. et al. Overexpression of NPC1L1 in the livers of transgenic Bama miniature pigs accelerates lipid peroxidation. Genes Genom 37, 183–191 (2015). https://doi.org/10.1007/s13258-014-0235-4

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