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The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis
Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolis...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450982/ https://www.ncbi.nlm.nih.gov/pubmed/37636398 http://dx.doi.org/10.1016/j.heliyon.2023.e19107 |
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author | Zhang, Qipeng Pan, Jilong Zhu, Yingying Liu, Jindi Pang, Yue Li, Jiarui Han, Pengju Gou, Meng Li, Jun Su, Peng Li, Qingwei Chi, Yan |
author_facet | Zhang, Qipeng Pan, Jilong Zhu, Yingying Liu, Jindi Pang, Yue Li, Jiarui Han, Pengju Gou, Meng Li, Jun Su, Peng Li, Qingwei Chi, Yan |
author_sort | Zhang, Qipeng |
collection | PubMed |
description | Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans. |
format | Online Article Text |
id | pubmed-10450982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104509822023-08-26 The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis Zhang, Qipeng Pan, Jilong Zhu, Yingying Liu, Jindi Pang, Yue Li, Jiarui Han, Pengju Gou, Meng Li, Jun Su, Peng Li, Qingwei Chi, Yan Heliyon Research Article Lamprey underwent biliary atresia (BA) at its metamorphosis stage. In contrast to patients with BA who develop progressive disease, lamprey can grow and develop normally, suggesting that lamprey has several adaptations for BA. Here we show that adaptive changes in bile acid and cholesterol metabolism are produced after lamprey BA. Among 1102 differentially expressed genes (DGEs) after BA in lamprey, many are enriched in gene ontology (GO) terms and pathways related to steroid metabolism. We find that among the DGEs related to bile acids and cholesterol metabolism, the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), sodium-dependent taurine cotransport polypeptide (NTCP) are significantly downregulated, whereas nuclear receptor farnesoid X receptor (FXR), multidrug resistance-associated protein 3 (MRP3), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), sterol O-acyltransferase 1 (SOAT1), and ATP binding cassette subfamily A member 1 (ABCA1) are remarkably upregulated. The changes in expression level are also validated by RT-qPCR. Furthermore, the level of high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in juvenile serum is higher compared to larvae. Taken together, the findings collectively indicate that after BA, lamprey may maintain bile acids and cholesterol homeostasis in liver tissue by inhibiting bile acids synthesis and uptake, promoting its efflux back to circulation, and enhancing cholesterol esterification for storage as lipid droplets and its egress to form nascent HDL (nHDL). Understanding the possible molecular mechanisms of lamprey metabolic adaptation sheds new light on the understanding of the development and treatment of diseases caused by abnormal bile acid and cholesterol metabolism in humans. Elsevier 2023-08-14 /pmc/articles/PMC10450982/ /pubmed/37636398 http://dx.doi.org/10.1016/j.heliyon.2023.e19107 Text en © 2023 The Authors 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 | Research Article Zhang, Qipeng Pan, Jilong Zhu, Yingying Liu, Jindi Pang, Yue Li, Jiarui Han, Pengju Gou, Meng Li, Jun Su, Peng Li, Qingwei Chi, Yan The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title | The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title_full | The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title_fullStr | The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title_full_unstemmed | The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title_short | The metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
title_sort | metabolic adaptation of bile acids and cholesterol after biliary atresia in lamprey via transcriptome-based analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10450982/ https://www.ncbi.nlm.nih.gov/pubmed/37636398 http://dx.doi.org/10.1016/j.heliyon.2023.e19107 |
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