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Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for...

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Autores principales: Huang, Yi-Long, Shen, Zhao-Qing, Huang, Chen-Hua, Teng, Yuan-Chi, Lin, Chao-Hsiung, Tsai, Ting-Fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066189/
https://www.ncbi.nlm.nih.gov/pubmed/33916843
http://dx.doi.org/10.3390/antiox10040559
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author Huang, Yi-Long
Shen, Zhao-Qing
Huang, Chen-Hua
Teng, Yuan-Chi
Lin, Chao-Hsiung
Tsai, Ting-Fen
author_facet Huang, Yi-Long
Shen, Zhao-Qing
Huang, Chen-Hua
Teng, Yuan-Chi
Lin, Chao-Hsiung
Tsai, Ting-Fen
author_sort Huang, Yi-Long
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for the development of treatments targeting NAFLD and NASH. Several discoveries are pinpointed. The first is that Cisd2 dosage modulates the severity of Western diet-induced (WD-induced) NAFLD. Specifically, Cisd2 haploinsufficiency accelerates NAFLD development and exacerbates progression toward NASH. Conversely, an enhanced Cisd2 copy number attenuates liver pathogenesis. Secondly, when a WD is fed to mice, transcriptomic analysis reveals that the major alterations affecting biological processes are related to inflammation, lipid metabolism, and DNA replication/repair. Thirdly, among these differentially expressed genes, the most significant changes involve Nrf2-mediated oxidative stress, cholesterol biosynthesis, and fatty acid metabolism. Finally, increased Cisd2 expression protects the liver from oxidative stress and reduces the occurrence of mitochondrial DNA deletions. Taken together, our mouse model reveals that Cisd2 plays a crucial role in protecting the liver from WD-induced damages. The development of therapeutic agents that effectively enhance Cisd2 expression is one potential approach to the treatment of WD-induced fatty liver diseases.
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spelling pubmed-80661892021-04-25 Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease Huang, Yi-Long Shen, Zhao-Qing Huang, Chen-Hua Teng, Yuan-Chi Lin, Chao-Hsiung Tsai, Ting-Fen Antioxidants (Basel) Article Nonalcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are the most common chronic liver diseases worldwide. However, drugs to treat NAFLD and NASH are an unmet clinical need. This study sought to provide evidence that Cisd2 is a molecular target for the development of treatments targeting NAFLD and NASH. Several discoveries are pinpointed. The first is that Cisd2 dosage modulates the severity of Western diet-induced (WD-induced) NAFLD. Specifically, Cisd2 haploinsufficiency accelerates NAFLD development and exacerbates progression toward NASH. Conversely, an enhanced Cisd2 copy number attenuates liver pathogenesis. Secondly, when a WD is fed to mice, transcriptomic analysis reveals that the major alterations affecting biological processes are related to inflammation, lipid metabolism, and DNA replication/repair. Thirdly, among these differentially expressed genes, the most significant changes involve Nrf2-mediated oxidative stress, cholesterol biosynthesis, and fatty acid metabolism. Finally, increased Cisd2 expression protects the liver from oxidative stress and reduces the occurrence of mitochondrial DNA deletions. Taken together, our mouse model reveals that Cisd2 plays a crucial role in protecting the liver from WD-induced damages. The development of therapeutic agents that effectively enhance Cisd2 expression is one potential approach to the treatment of WD-induced fatty liver diseases. MDPI 2021-04-03 /pmc/articles/PMC8066189/ /pubmed/33916843 http://dx.doi.org/10.3390/antiox10040559 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Yi-Long
Shen, Zhao-Qing
Huang, Chen-Hua
Teng, Yuan-Chi
Lin, Chao-Hsiung
Tsai, Ting-Fen
Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title_full Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title_fullStr Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title_full_unstemmed Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title_short Cisd2 Protects the Liver from Oxidative Stress and Ameliorates Western Diet-Induced Nonalcoholic Fatty Liver Disease
title_sort cisd2 protects the liver from oxidative stress and ameliorates western diet-induced nonalcoholic fatty liver disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066189/
https://www.ncbi.nlm.nih.gov/pubmed/33916843
http://dx.doi.org/10.3390/antiox10040559
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