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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
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.
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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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