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Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish
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 accumula...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263516/ https://www.ncbi.nlm.nih.gov/pubmed/35811843 http://dx.doi.org/10.1016/j.isci.2022.104670 |
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author | Cao, Xiufei Fang, Wei Li, Xueshan Wang, Xiuneng Mai, Kangsen Ai, Qinghui |
author_facet | Cao, Xiufei Fang, Wei Li, Xueshan Wang, Xiuneng Mai, Kangsen Ai, Qinghui |
author_sort | Cao, Xiufei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9263516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92635162022-07-09 Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish Cao, Xiufei Fang, Wei Li, Xueshan Wang, Xiuneng Mai, Kangsen Ai, Qinghui iScience Article 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. Elsevier 2022-06-26 /pmc/articles/PMC9263516/ /pubmed/35811843 http://dx.doi.org/10.1016/j.isci.2022.104670 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Cao, Xiufei Fang, Wei Li, Xueshan Wang, Xiuneng Mai, Kangsen Ai, Qinghui Increased LDL receptor by SREBP2 or SREBP2-induced lncRNA LDLR-AS promotes triglyceride accumulation in fish |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263516/ https://www.ncbi.nlm.nih.gov/pubmed/35811843 http://dx.doi.org/10.1016/j.isci.2022.104670 |
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