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Simões, I.C.M.* ; Karkucinska‐wieckowska, A.* ; Janikiewicz, J.* ; Szymanska, S.* ; Pronicki, M.* ; Dobrzyn, P.* ; Dabrowski, M.* ; Dobrzyn, A.* ; Oliveira, P.J.* ; Zischka, H. ; Potes, Y.* ; Wieckowski, M.R.*

Western diet causes obesity-induced nonalcoholic fatty liver disease development by differentially compromising the autophagic response.

Antioxidants 9:995 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Mitochondria ; Oxidative Stress ; Peroxisomes ; Autophagy ; Steatosis; Hepatic Steatosis; Cardiolipin; Damage; Lipotoxicity; Mitochondria; Pathogenesis; Peroxisomes; Stress; Humans; Cycle
ISSN (print) / ISBN 2076-3921
e-ISSN 2076-3921
Zeitschrift Antioxidants
Quellenangaben Band: 9, Heft: 10, Seiten: , Artikelnummer: 995 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)
Förderungen Deutsche Forschungsgemeinschaft (DFG)
FEDER funds through the Operational Program Competitiveness Factors COMPETE
Foundation for Science and Technology (FCT)
FOIE GRAS
mtFOIE GRAS
European Union's Horizon 2020 Research and Innovation program under the Marie Sklodowska-Curie Grant
National Science Centre, Poland