Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish
Summary: LDLR, as the uptake receptor of low-density lipoprotein, plays a crucial role in lipid metabolism. However, the detailed mechanism by which LDLR affects hepatic triglyceride (TG) accumulation has rarely been reported. Here, we found that knockdown of LDLR effectively mitigated PA-induced TG...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222009427 |
| _version_ | 1828331893150449664 |
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| author | Xiufei Cao Wei Fang Xueshan Li Xiuneng Wang Kangsen Mai Qinghui Ai |
| author_facet | Xiufei Cao Wei Fang Xueshan Li Xiuneng Wang Kangsen Mai Qinghui Ai |
| author_sort | Xiufei Cao |
| collection | DOAJ |
| description | Summary: LDLR, as the uptake receptor of low-density lipoprotein, plays a crucial role in lipid metabolism. However, the detailed mechanism by which LDLR affects hepatic triglyceride (TG) accumulation has rarely been reported. Here, we found that knockdown of LDLR effectively mitigated PA-induced TG accumulation. Further analysis revealed that the expression of LDLR was controlled by SREBP2 directly and indirectly. On one hand, transcription factor SREBP2 activated the transcription of LDLR directly. On the other hand, SREBP2 indirectly regulated LDLR by increasing the transcription of lncRNA LDLR-AS in fish. Mechanism analysis found that LDLR-AS functioned as an RNA scaffold to recruit heterogeneous nuclear ribonucleoprotein R (hnRNPR) to the 5′ UTR region of LDLR mRNA, which stabilized LDLR mRNA at the post-transcription level. In conclusion, our study demonstrates that increased LDLR transcription and mRNA stability is regulated by SREBP2 directly or indirectly, and promotes hepatic TG accumulation by endocytosing LDL in fish. |
| first_indexed | 2024-04-13T20:58:28Z |
| format | Article |
| id | doaj.art-d1e54dad37eb47deb6f1d2dfc4eaad48 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T20:58:28Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d1e54dad37eb47deb6f1d2dfc4eaad482022-12-22T02:30:13ZengElsevieriScience2589-00422022-07-01257104670Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fishXiufei Cao0Wei Fang1Xueshan Li2Xiuneng Wang3Kangsen Mai4Qinghui Ai5Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao, Shandong 266237, People’s Republic of ChinaKey Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, Qingdao, Shandong 266003, People’s Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao, Shandong 266237, People’s Republic of China; Corresponding authorSummary: LDLR, as the uptake receptor of low-density lipoprotein, plays a crucial role in lipid metabolism. However, the detailed mechanism by which LDLR affects hepatic triglyceride (TG) accumulation has rarely been reported. Here, we found that knockdown of LDLR effectively mitigated PA-induced TG accumulation. Further analysis revealed that the expression of LDLR was controlled by SREBP2 directly and indirectly. On one hand, transcription factor SREBP2 activated the transcription of LDLR directly. On the other hand, SREBP2 indirectly regulated LDLR by increasing the transcription of lncRNA LDLR-AS in fish. Mechanism analysis found that LDLR-AS functioned as an RNA scaffold to recruit heterogeneous nuclear ribonucleoprotein R (hnRNPR) to the 5′ UTR region of LDLR mRNA, which stabilized LDLR mRNA at the post-transcription level. In conclusion, our study demonstrates that increased LDLR transcription and mRNA stability is regulated by SREBP2 directly or indirectly, and promotes hepatic TG accumulation by endocytosing LDL in fish.http://www.sciencedirect.com/science/article/pii/S2589004222009427Biological sciencesZoologyCell biologyFunctional aspects of cell biology |
| spellingShingle | Xiufei Cao Wei Fang Xueshan Li Xiuneng Wang Kangsen Mai Qinghui Ai Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish iScience Biological sciences Zoology Cell biology Functional aspects of cell biology |
| title | Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
| title_full | Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
| title_fullStr | Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
| title_full_unstemmed | Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
| title_short | Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
| title_sort | increased ldl receptor by srebp2 or srebp2 induced lncrna ldlr as promotes triglyceride accumulation in fish |
| topic | Biological sciences Zoology Cell biology Functional aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222009427 |
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