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Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. In addition, NAFLD may increase the risk of cardiovascular and liver-related diseases, and displays features of metabolic syndrome. In NAFLD, oxidative stress is primarily caused by excessive fr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855157/ https://www.ncbi.nlm.nih.gov/pubmed/36670871 http://dx.doi.org/10.3390/antiox12010009 |
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author | Park, Jiyoung Kim, Nam Hee Yi, Ho Jin Rhee, Sue Goo Woo, Hyun Ae |
author_facet | Park, Jiyoung Kim, Nam Hee Yi, Ho Jin Rhee, Sue Goo Woo, Hyun Ae |
author_sort | Park, Jiyoung |
collection | PubMed |
description | Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. In addition, NAFLD may increase the risk of cardiovascular and liver-related diseases, and displays features of metabolic syndrome. In NAFLD, oxidative stress is primarily caused by excessive free fatty acids. The oxidation of fatty acids is usually caused by β-oxidation of mitochondria under normal conditions, resulting in the production of energy. However, when the inflow of fatty acids in NAFLD becomes excessive, the β-oxidation of mitochondria becomes saturated and the oxidation process increases at sites including peroxisomes and microsomes, thereby increasing production of reactive oxygen species (ROS). Thus, hepatic mitochondrial ROS play an important role in the pathogenesis of NAFLD. Eliminating mitochondrial ROS may improve NAFLD, but the underlying mechanism remains unclear. We examined the effect of mitochondrial ROS on NAFLD by focusing on peroxiredoxin (Prx), an antioxidant protein that can remove hydrogen peroxide. The protective effect and pathological phenomenon of mitochondrial peroxiredoxin in methionine-choline deficient diet (MCD)-induced liver injury was assessed in a mouse model of NAFLD. In these mice, mitochondrial peroxiredoxin deficiency significantly increased hepatic steatosis and fibrosis. In addition, ablation of Prx III enhances susceptibility to MCD diet-induced oxidative stress and exacerbates NAFLD progression by promoting inflammation. The binding assay results also showed that Prx III-deficient mice had more severe liver damage than Prx III-abundant mice in MCD diet liver injury models. The present data suggest that mitochondrial peroxiredoxin III could be a therapeutic target for preventing and suppressing diet-induced NAFLD. |
format | Online Article Text |
id | pubmed-9855157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98551572023-01-21 Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet Park, Jiyoung Kim, Nam Hee Yi, Ho Jin Rhee, Sue Goo Woo, Hyun Ae Antioxidants (Basel) Article Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. In addition, NAFLD may increase the risk of cardiovascular and liver-related diseases, and displays features of metabolic syndrome. In NAFLD, oxidative stress is primarily caused by excessive free fatty acids. The oxidation of fatty acids is usually caused by β-oxidation of mitochondria under normal conditions, resulting in the production of energy. However, when the inflow of fatty acids in NAFLD becomes excessive, the β-oxidation of mitochondria becomes saturated and the oxidation process increases at sites including peroxisomes and microsomes, thereby increasing production of reactive oxygen species (ROS). Thus, hepatic mitochondrial ROS play an important role in the pathogenesis of NAFLD. Eliminating mitochondrial ROS may improve NAFLD, but the underlying mechanism remains unclear. We examined the effect of mitochondrial ROS on NAFLD by focusing on peroxiredoxin (Prx), an antioxidant protein that can remove hydrogen peroxide. The protective effect and pathological phenomenon of mitochondrial peroxiredoxin in methionine-choline deficient diet (MCD)-induced liver injury was assessed in a mouse model of NAFLD. In these mice, mitochondrial peroxiredoxin deficiency significantly increased hepatic steatosis and fibrosis. In addition, ablation of Prx III enhances susceptibility to MCD diet-induced oxidative stress and exacerbates NAFLD progression by promoting inflammation. The binding assay results also showed that Prx III-deficient mice had more severe liver damage than Prx III-abundant mice in MCD diet liver injury models. The present data suggest that mitochondrial peroxiredoxin III could be a therapeutic target for preventing and suppressing diet-induced NAFLD. MDPI 2022-12-21 /pmc/articles/PMC9855157/ /pubmed/36670871 http://dx.doi.org/10.3390/antiox12010009 Text en © 2022 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 Park, Jiyoung Kim, Nam Hee Yi, Ho Jin Rhee, Sue Goo Woo, Hyun Ae Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title | Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title_full | Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title_fullStr | Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title_full_unstemmed | Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title_short | Mitochondrial Peroxiredoxin III Protects against Non-Alcoholic Fatty Liver Disease Caused by a Methionine-Choline Deficient Diet |
title_sort | mitochondrial peroxiredoxin iii protects against non-alcoholic fatty liver disease caused by a methionine-choline deficient diet |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855157/ https://www.ncbi.nlm.nih.gov/pubmed/36670871 http://dx.doi.org/10.3390/antiox12010009 |
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