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

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• 作者：Chongli Xu (1) (2)
  Yu Liu (3)
  Yuchen Gong (4)
  Xinping Duan (1)
  Xiaochun Tang (1)
  Mingjun Zhang (1)
  Daxin Pang (1)
  Liqing Yu (5)
  Hong Wei (3)
  Hongsheng Ouyang (1)
  
  1. Jilin Provincial Key Laboratory of Animal Embryo Engineering ; College of Animal Sciences ; Jilin University ; 5333 Xi An DaLu ; Changchun ; 130062 ; People鈥檚 Republic of China
  2. College of Chemical Engineering and Biotechnology ; Jilin Institute of Chemical Technology ; 45 ChengDe Road ; Jilin ; 132022 ; People鈥檚 Republic of China
  3. Department of Laboratory Animal Science ; College of Basic Medicine ; Third Military Medical University ; Chongqing ; 400038 ; People鈥檚 Republic of China
  4. College of Animal Science ; Jilin Agricultural University ; Changchun ; 130118 ; People鈥檚 Republic of China
  5. Department of Animal and Avian Sciences ; University of Maryland ; College Park ; 20742 ; Maryland ; USA
  
• 关键词：Niemann ; Pick C1 Like 1 (NPC1L1) ; Overexpression ; Nuclear transfer ; Transcription ; Lipid peroxidation
• 刊名：Genes & Genomics
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：37
• 期：2
• 页码：183-191
• 全文大小：1,105 KB
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• 刊物主题：Microbial Genetics and Genomics; Plant Genetics & Genomics; Animal Genetics and Genomics; Human Genetics;
• 出版者：Springer Netherlands
• ISSN：2092-9293

文摘

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.