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

        Chongli Xu,Yu Liu,Yuchen Gong,Xinping Duan,Xiaochun Tang,Mingjun Zhang,Daxin Pang,Liqing Yu,Hongwei Zhao,Hongsheng Ouyang 한국유전학회 2015 Genes & Genomics Vol.37 No.2

        Although Niemann-Pick C1-Like 1 (NPC1L1)plays a key role in intestinal cholesterol absorption, regulatingcholesterol metabolism and maintaining cholesterolmetabolic homeostasis, the molecular mechanism ofNPC1L1 in lipid-metabolism disorders leading to liverdisease remains largely unknown. Previous studies haveshown that NPC1L1 is related with the development offatty liver. Therefore, we hypothesized that NPC1L1 playsan important role in lipid-metabolism disorders and liverdisease by affecting the transcription of certain genesinvolved in lipid synthesis. To further elucidate the functionof NPC1L1, especially in the liver, we used somaticcellnuclear transfer to establish transgenic pigs thatexpressed human NPC1L1 in their livers. We investigatedsuperoxide dismutase activities and the levels of free fattyacids and malondialdehyde, a biomarker of lipid peroxidation. Superoxide dismutase activities significantlydecreased, and free fatty acid and malondialdehyde levelssignificantly increased in the NPC1L1 transgenic pigs,indicating that the overexpression of NPC1L1 in the liverresulted in severe lipid peroxidation. Our findings suggestthat NPC1L1 plays an important role in lipid-metabolismdisorders and liver disease.

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