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Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725223/ https://www.ncbi.nlm.nih.gov/pubmed/29220698 http://dx.doi.org/10.1016/j.redox.2017.11.016 |
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author | Bellanti, Francesco Villani, Rosanna Tamborra, Rosanna Blonda, Maria Iannelli, Giuseppina di Bello, Giorgia Facciorusso, Antonio Poli, Giuseppe Iuliano, Luigi Avolio, Carlo Vendemiale, Gianluigi Serviddio, Gaetano |
author_facet | Bellanti, Francesco Villani, Rosanna Tamborra, Rosanna Blonda, Maria Iannelli, Giuseppina di Bello, Giorgia Facciorusso, Antonio Poli, Giuseppe Iuliano, Luigi Avolio, Carlo Vendemiale, Gianluigi Serviddio, Gaetano |
author_sort | Bellanti, Francesco |
collection | PubMed |
description | The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury. |
format | Online Article Text |
id | pubmed-5725223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57252232017-12-18 Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression Bellanti, Francesco Villani, Rosanna Tamborra, Rosanna Blonda, Maria Iannelli, Giuseppina di Bello, Giorgia Facciorusso, Antonio Poli, Giuseppe Iuliano, Luigi Avolio, Carlo Vendemiale, Gianluigi Serviddio, Gaetano Redox Biol Research Paper The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury. Elsevier 2017-12-05 /pmc/articles/PMC5725223/ /pubmed/29220698 http://dx.doi.org/10.1016/j.redox.2017.11.016 Text en © 2017 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Bellanti, Francesco Villani, Rosanna Tamborra, Rosanna Blonda, Maria Iannelli, Giuseppina di Bello, Giorgia Facciorusso, Antonio Poli, Giuseppe Iuliano, Luigi Avolio, Carlo Vendemiale, Gianluigi Serviddio, Gaetano Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title_full | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title_fullStr | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title_full_unstemmed | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title_short | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
title_sort | synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725223/ https://www.ncbi.nlm.nih.gov/pubmed/29220698 http://dx.doi.org/10.1016/j.redox.2017.11.016 |
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