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

• Published in: Genes & genomics 2015, 37(2), , pp.183-191
• Main Authors: Xu, C., Jilin University, Changchun, Peoples Republic of China, Liu, Y., Third Military Medical University, Peoples Republic of China, Gong, Y., Jilin Agricultural University, Changchun, Peoples Republic of China, Duan, X., Jilin University, Changchun, Peoples Republic of China, Tang, X., Jilin University, Changchun, Peoples Republic of China, Zhang, M., Jilin University, Changchun, Peoples Republic of China, Pang, D., Jilin University, Changchun, Peoples Republic of China, Yu, L., University of Maryland, Maryland, USA, Wei, H., Third Military Medical University, Peoples Republic of China, Ouyang, H., Jilin University, Changchun, Peoples Republic of China
• Format: Article
• Language: English
• Subjects: absorption; Animal Genetics and Genomics; biomarkers; Biomedical and Life Sciences; cholesterol; cholesterol metabolism; fatty liver; free fatty acids; gene overexpression; genes; genetically modified organisms; homeostasis; Human Genetics; humans; Life Sciences; LIPID PEROXIDATION; liver; malondialdehyde; Microbial Genetics and Genomics; miniature swine; Niemann-Pick C1 Like 1 (NPC1L1),Overexpression,Nuclear transfer; PEROXIDACION LIPIDICA; PEROXYDATION DES LIPIDES; Plant Genetics and Genomics; Research Article; superoxide dismutase; swine; TRANSCRIPCION; TRANSCRIPTION; 생물학
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-014-0235-4

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.