Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/94311
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Health Technology and Informatics | - |
dc.creator | Lin, H | - |
dc.creator | Wang, L | - |
dc.creator | Liu, Z | - |
dc.creator | Long, K | - |
dc.creator | Kong, M | - |
dc.creator | Ye, D | - |
dc.creator | Chen, X | - |
dc.creator | Wang, K | - |
dc.creator | Wu, KKL | - |
dc.creator | Fan, M | - |
dc.creator | Song, E | - |
dc.creator | Wang, C | - |
dc.creator | Hoo, RLC | - |
dc.creator | Hui, X | - |
dc.creator | Hallenborg, P | - |
dc.creator | Piao, H | - |
dc.creator | Xu, A | - |
dc.creator | Cheng, KKY | - |
dc.date.accessioned | 2022-08-11T02:01:49Z | - |
dc.date.available | 2022-08-11T02:01:49Z | - |
dc.identifier.issn | 2198-3844 | - |
dc.identifier.uri | http://hdl.handle.net/10397/94311 | - |
dc.language.iso | en | en_US |
dc.publisher | Wiley-VCH | en_US |
dc.rights | © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH. | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | en_US |
dc.rights | The following publication Lin, H., Wang, L., Liu, Z., Long, K., Kong, M., Ye, D., ... & Cheng, K. K. (2022). Hepatic MDM2 Causes Metabolic Associated Fatty Liver Disease by Blocking Triglyceride‐VLDL Secretion via ApoB Degradation. Advanced Science, 9(20), 2200742 is available at https://doi.org/10.1002/advs.202200742 | en_US |
dc.subject | Apolipoprotein B (ApoB) | en_US |
dc.subject | Metabolic associated fatty liver | en_US |
dc.subject | Murine double minute 2 (MDM2) | en_US |
dc.subject | Obesity | en_US |
dc.subject | Triglyceride-VLDL | en_US |
dc.title | Hepatic MDM2 causes metabolic associated fatty liver disease by blocking triglyceride-VLDL secretion via ApoB degradation | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.volume | 9 | - |
dc.identifier.issue | 20 | - |
dc.identifier.doi | 10.1002/advs.202200742 | - |
dcterms.abstract | Dysfunctional triglyceride-very low-density lipoprotein (TG-VLDL) metabolism is linked to metabolic-associated fatty liver disease (MAFLD); however, the underlying cause remains unclear. The study shows that hepatic E3 ubiquitin ligase murine double minute 2 (MDM2) controls MAFLD by blocking TG-VLDL secretion. A remarkable upregulation of MDM2 is observed in the livers of human and mouse models with different levels of severity of MAFLD. Hepatocyte-specific deletion of MDM2 protects against high-fat high-cholesterol diet-induced hepatic steatosis and inflammation, accompanied by a significant elevation in TG-VLDL secretion. As an E3 ubiquitin ligase, MDM2 targets apolipoprotein B (ApoB) for proteasomal degradation through direct protein–protein interaction, which leads to reduced TG-VLDL secretion in hepatocytes. Pharmacological blockage of the MDM2-ApoB interaction alleviates dietary-induced hepatic steatohepatitis and fibrosis by inducing hepatic ApoB expression and subsequent TG-VLDL secretion. The effect of MDM2 on VLDL metabolism is p53-independent. Collectively, these findings suggest that MDM2 acts as a negative regulator of hepatic ApoB levels and TG-VLDL secretion in MAFLD. Inhibition of the MDM2-ApoB interaction may represent a potential therapeutic approach for MAFLD treatment. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Advanced science, 15 July 2022, v. 9, no. 20, 2200742 | - |
dcterms.isPartOf | Advanced science | - |
dcterms.issued | 2022-07 | - |
dc.identifier.scopus | 2-s2.0-85129433641 | - |
dc.identifier.pmid | 35524581 | - |
dc.identifier.artn | 2200742 | - |
dc.description.validate | 202208 bckw | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | a1638 | en_US |
dc.identifier.SubFormID | 45714 | en_US |
dc.description.fundingSource | RGC | en_US |
dc.description.pubStatus | Published | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
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Lin_Hepatic_Metabolic_Associated.pdf | 6.52 MB | Adobe PDF | View/Open |
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