Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/105529
Title: Western Diet Causes Obesity-Induced Nonalcoholic Fatty Liver Disease Development by Differentially Compromising the Autophagic Response
Authors: Simoes, Ines C M
Karkucinska-Wieckowska, Agnieszka
Janikiewicz, Justyna
Szymanska, Sylwia
Pronicki, Maciej
Dobrzyn, Pawel
Dabrowski, Michal
Dobrzyn, Agnieszka
Oliveira, Paulo J. 
Zischka, Hans
Potes, Yaiza
Wieckowski, Mariusz R. 
Keywords: mitochondria; oxidative stress; peroxisomes; autophagy; steatosis
Issue Date: 15-Oct-2020
Publisher: MDPI
Project: National Science Centre, Poland (UMO-2018/29/B/NZ1/00589) 
Deutsche Forschungsgemeinschaft (DFG) (Grant ZI1386/2-1) 
PTDC/ASP-HOR/29152/2017 
POCI-01-0145-FEDER-029152 
UIDB/04539/2020 
Marie Skłodowska-Curie Grant Agreement No. 722619 (FOIE GRAS) 
Marie Skłodowska-Curie Grant Agreement No. 734719 (mtFOIE GRAS) 
Serial title, monograph or event: Antioxidants
Volume: 9
Issue: 10
Abstract: 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.
URI: https://hdl.handle.net/10316/105529
ISSN: 2076-3921
DOI: 10.3390/antiox9100995
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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