A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model
The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we to...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2016-07-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/5/7/979 |
| _version_ | 1830308447807078400 |
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| author | Hong Yu Wang Chao Quan Chunxiu Hu Bingxian Xie Yinan Du Liang Chen Wei Yang Liu Yang Qiaoli Chen Bin Shen Bian Hu Zhihong Zheng Haibo Zhu Xingxu Huang Guowang Xu Shuai Chen |
| author_facet | Hong Yu Wang Chao Quan Chunxiu Hu Bingxian Xie Yinan Du Liang Chen Wei Yang Liu Yang Qiaoli Chen Bin Shen Bian Hu Zhihong Zheng Haibo Zhu Xingxu Huang Guowang Xu Shuai Chen |
| author_sort | Hong Yu Wang |
| collection | DOAJ |
| description | The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we took a genetic approach to delete the LDLR in rats aiming to increase plasma LDL cholesterol (LDL-C). An LDLR knockout rat was generated via zinc-finger nuclease technology, which harbors a 19-basepair deletion in the seventh exon of the ldlr gene. As expected, deletion of the LDLR elevated total cholesterol and total triglyceride in the plasma, and caused a tenfold increase of plasma LDL-C and a fourfold increase of plasma very low-density lipoprotein (VLDL-C). A lipidomics analysis revealed that deletion of the LDLR affected hepatic lipid metabolism, particularly lysophosphatidylcholines, free fatty acids and sphingolipids in the liver. Cholesterol ester (CE) 20:4 also displayed a significant increase in the LDLR knockout rats. Taken together, the LDLR knockout rat offers a new model of hypercholesterolemia, and the lipidomics analysis reveals hepatic lipid signatures associating with deficiency of the LDL receptor. |
| first_indexed | 2024-12-19T10:50:10Z |
| format | Article |
| id | doaj.art-e0974a0d29bc4a958ba1fd381a32c16c |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T10:50:10Z |
| publishDate | 2016-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-e0974a0d29bc4a958ba1fd381a32c16c2022-12-21T20:25:03ZengThe Company of BiologistsBiology Open2046-63902016-07-015797998610.1242/bio.019802019802A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat modelHong Yu Wang0Chao Quan1Chunxiu Hu2Bingxian Xie3Yinan Du4Liang Chen5Wei Yang6Liu Yang7Qiaoli Chen8Bin Shen9Bian Hu10Zhihong Zheng11Haibo Zhu12Xingxu Huang13Guowang Xu14Shuai Chen15 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China Laboratory Animal Center, China Medical University, Shenyang 110001, China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China Laboratory Animal Center, China Medical University, Shenyang 110001, China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we took a genetic approach to delete the LDLR in rats aiming to increase plasma LDL cholesterol (LDL-C). An LDLR knockout rat was generated via zinc-finger nuclease technology, which harbors a 19-basepair deletion in the seventh exon of the ldlr gene. As expected, deletion of the LDLR elevated total cholesterol and total triglyceride in the plasma, and caused a tenfold increase of plasma LDL-C and a fourfold increase of plasma very low-density lipoprotein (VLDL-C). A lipidomics analysis revealed that deletion of the LDLR affected hepatic lipid metabolism, particularly lysophosphatidylcholines, free fatty acids and sphingolipids in the liver. Cholesterol ester (CE) 20:4 also displayed a significant increase in the LDLR knockout rats. Taken together, the LDLR knockout rat offers a new model of hypercholesterolemia, and the lipidomics analysis reveals hepatic lipid signatures associating with deficiency of the LDL receptor.http://bio.biologists.org/content/5/7/979Low-density lipoprotein receptor (LDLR)CholesterolLipid metabolismRatKnockout |
| spellingShingle | Hong Yu Wang Chao Quan Chunxiu Hu Bingxian Xie Yinan Du Liang Chen Wei Yang Liu Yang Qiaoli Chen Bin Shen Bian Hu Zhihong Zheng Haibo Zhu Xingxu Huang Guowang Xu Shuai Chen A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model Biology Open Low-density lipoprotein receptor (LDLR) Cholesterol Lipid metabolism Rat Knockout |
| title | A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model |
| title_full | A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model |
| title_fullStr | A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model |
| title_full_unstemmed | A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model |
| title_short | A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model |
| title_sort | lipidomics study reveals hepatic lipid signatures associating with deficiency of the ldl receptor in a rat model |
| topic | Low-density lipoprotein receptor (LDLR) Cholesterol Lipid metabolism Rat Knockout |
| url | http://bio.biologists.org/content/5/7/979 |
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