Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response
Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative s...
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doaj-19864496d3dd43d88c771bc5876e8caf2020-11-25T03:44:27ZengMDPI AGAntioxidants2076-39212020-10-01999599510.3390/antiox9100995Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic ResponseInes C. M. Simoes0Agnieszka Karkucinska-Wieckowska1Justyna Janikiewicz2Sylwia Szymanska3Maciej Pronicki4Pawel Dobrzyn5Michal Dabrowski6Agnieszka Dobrzyn7Paulo J. Oliveira8Hans Zischka9Yaiza Potes10Mariusz R. Wieckowski11Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandCNC-Center for Neuroscience and Cell Biology, UC-Biotech, University of Coimbra, Biocant Park, 3060-197 Cantanhede, PortugalInstitute of Toxicology and Environmental Hygiene, School of Medicine, Technical University Munich, D-80802 Munich, GermanyNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandNencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, PolandNonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression.https://www.mdpi.com/2076-3921/9/10/995mitochondriaoxidative stressperoxisomesautophagysteatosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ines C. M. Simoes Agnieszka Karkucinska-Wieckowska Justyna Janikiewicz Sylwia Szymanska Maciej Pronicki Pawel Dobrzyn Michal Dabrowski Agnieszka Dobrzyn Paulo J. Oliveira Hans Zischka Yaiza Potes Mariusz R. Wieckowski |
spellingShingle |
Ines C. M. Simoes Agnieszka Karkucinska-Wieckowska Justyna Janikiewicz Sylwia Szymanska Maciej Pronicki Pawel Dobrzyn Michal Dabrowski Agnieszka Dobrzyn Paulo J. Oliveira Hans Zischka Yaiza Potes Mariusz R. Wieckowski Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response Antioxidants mitochondria oxidative stress peroxisomes autophagy steatosis |
author_facet |
Ines C. M. Simoes Agnieszka Karkucinska-Wieckowska Justyna Janikiewicz Sylwia Szymanska Maciej Pronicki Pawel Dobrzyn Michal Dabrowski Agnieszka Dobrzyn Paulo J. Oliveira Hans Zischka Yaiza Potes Mariusz R. Wieckowski |
author_sort |
Ines C. M. Simoes |
title |
Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response |
title_short |
Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response |
title_full |
Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response |
title_fullStr |
Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response |
title_full_unstemmed |
Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response |
title_sort |
western diet causes obesity-induced nonalcoholic fatty liver disease development by differentially compromising the autophagic response |
publisher |
MDPI AG |
series |
Antioxidants |
issn |
2076-3921 |
publishDate |
2020-10-01 |
description |
Nonalcoholic fatty liver disease (NAFLD) is characterized by the development of steatosis, which can ultimately compromise liver function. Mitochondria are key players in obesity-induced metabolic disorders; however, the distinct role of hypercaloric diet constituents in hepatic cellular oxidative stress and metabolism is unknown. Male mice were fed either a high-fat (HF) diet, a high-sucrose (HS) diet or a combined HF plus HS (HFHS) diet for 16 weeks. This study shows that hypercaloric diets caused steatosis; however, the HFHS diet induced severe fibrotic phenotype. At the mitochondrial level, lipidomic analysis showed an increased cardiolipin content for all tested diets. Despite this, no alterations were found in the coupling efficiency of oxidative phosphorylation and neither in mitochondrial fatty acid oxidation (FAO). Consistent with unchanged mitochondrial function, no alterations in mitochondrial-induced reactive oxygen species (ROS) and antioxidant capacity were found. In contrast, the HF and HS diets caused lipid peroxidation and provoked altered antioxidant enzyme levels/activities in liver tissue. Our work provides evidence that hepatic oxidative damage may be caused by augmented levels of peroxisomes and consequently higher peroxisomal FAO-induced ROS in the early NAFLD stage. Hepatic damage is also associated with autophagic flux impairment, which was demonstrated to be diet-type dependent. The HS diet induced a reduction in autophagosomal formation, while the HF diet reduced levels of cathepsins. The accumulation of damaged organelles could instigate hepatocyte injuries and NAFLD progression. |
topic |
mitochondria oxidative stress peroxisomes autophagy steatosis |
url |
https://www.mdpi.com/2076-3921/9/10/995 |
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