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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...

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Autores principales: Park, Jiyoung, Kim, Nam Hee, Yi, Ho Jin, Rhee, Sue Goo, Woo, Hyun Ae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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