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The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production

The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed w...

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Autores principales: Simões, Inês C. M., Amorim, Ricardo, Teixeira, José, Karkucinska-Wieckowska, Agnieszka, Carvalho, Adriana, Pereira, Susana P., Simões, Rui F., Szymanska, Sylwia, Dąbrowski, Michał, Janikiewicz, Justyna, Dobrzyń, Agnieszka, Oliveira, Paulo J., Potes, Yaiza, Wieckowski, Mariusz R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268944/
https://www.ncbi.nlm.nih.gov/pubmed/34202179
http://dx.doi.org/10.3390/ijms22136848
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author Simões, Inês C. M.
Amorim, Ricardo
Teixeira, José
Karkucinska-Wieckowska, Agnieszka
Carvalho, Adriana
Pereira, Susana P.
Simões, Rui F.
Szymanska, Sylwia
Dąbrowski, Michał
Janikiewicz, Justyna
Dobrzyń, Agnieszka
Oliveira, Paulo J.
Potes, Yaiza
Wieckowski, Mariusz R.
author_facet Simões, Inês C. M.
Amorim, Ricardo
Teixeira, José
Karkucinska-Wieckowska, Agnieszka
Carvalho, Adriana
Pereira, Susana P.
Simões, Rui F.
Szymanska, Sylwia
Dąbrowski, Michał
Janikiewicz, Justyna
Dobrzyń, Agnieszka
Oliveira, Paulo J.
Potes, Yaiza
Wieckowski, Mariusz R.
author_sort Simões, Inês C. M.
collection PubMed
description The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed with a high-fat plus high-sucrose diet for 16, 20, 22, and 24 weeks to induce NAFL. Up to the 20th week, an early mitochondrial remodeling with increased OXPHOS subunits levels and higher mitochondrial respiration occurred. Interestingly, a progressive loss of mitochondrial respiration along “Western diet” feeding was identified, accompanied by higher susceptibility to mitochondrial permeability transition pore opening. Importantly, our findings prove that mitochondrial alterations and subsequent impairment are independent of an excessive mitochondrial reactive oxygen species (ROS) generation, which was found to be progressively diminished along with disease progression. Instead, increased peroxisomal abundance and peroxisomal fatty acid oxidation-related pathway suggest that peroxisomes may contribute to hepatic ROS generation and oxidative damage, which may accelerate hepatic injury and disease progression. We show here for the first time the sequential events of mitochondrial alterations involved in non-alcoholic fatty liver disease (NAFLD) progression and demonstrate that mitochondrial ROS are not one of the first hits that cause NAFLD progression.
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spelling pubmed-82689442021-07-10 The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production Simões, Inês C. M. Amorim, Ricardo Teixeira, José Karkucinska-Wieckowska, Agnieszka Carvalho, Adriana Pereira, Susana P. Simões, Rui F. Szymanska, Sylwia Dąbrowski, Michał Janikiewicz, Justyna Dobrzyń, Agnieszka Oliveira, Paulo J. Potes, Yaiza Wieckowski, Mariusz R. Int J Mol Sci Article The progression of non-alcoholic fatty liver (NAFL) into non-alcoholic steatohepatitis implicates multiple mechanisms, chief of which is mitochondrial dysfunction. However, the sequence of events underlying mitochondrial failure are still poorly clarified. In this work, male C57BL/6J mice were fed with a high-fat plus high-sucrose diet for 16, 20, 22, and 24 weeks to induce NAFL. Up to the 20th week, an early mitochondrial remodeling with increased OXPHOS subunits levels and higher mitochondrial respiration occurred. Interestingly, a progressive loss of mitochondrial respiration along “Western diet” feeding was identified, accompanied by higher susceptibility to mitochondrial permeability transition pore opening. Importantly, our findings prove that mitochondrial alterations and subsequent impairment are independent of an excessive mitochondrial reactive oxygen species (ROS) generation, which was found to be progressively diminished along with disease progression. Instead, increased peroxisomal abundance and peroxisomal fatty acid oxidation-related pathway suggest that peroxisomes may contribute to hepatic ROS generation and oxidative damage, which may accelerate hepatic injury and disease progression. We show here for the first time the sequential events of mitochondrial alterations involved in non-alcoholic fatty liver disease (NAFLD) progression and demonstrate that mitochondrial ROS are not one of the first hits that cause NAFLD progression. MDPI 2021-06-25 /pmc/articles/PMC8268944/ /pubmed/34202179 http://dx.doi.org/10.3390/ijms22136848 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
Simões, Inês C. M.
Amorim, Ricardo
Teixeira, José
Karkucinska-Wieckowska, Agnieszka
Carvalho, Adriana
Pereira, Susana P.
Simões, Rui F.
Szymanska, Sylwia
Dąbrowski, Michał
Janikiewicz, Justyna
Dobrzyń, Agnieszka
Oliveira, Paulo J.
Potes, Yaiza
Wieckowski, Mariusz R.
The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title_full The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title_fullStr The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title_full_unstemmed The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title_short The Alterations of Mitochondrial Function during NAFLD Progression—An Independent Effect of Mitochondrial ROS Production
title_sort alterations of mitochondrial function during nafld progression—an independent effect of mitochondrial ros production
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268944/
https://www.ncbi.nlm.nih.gov/pubmed/34202179
http://dx.doi.org/10.3390/ijms22136848
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