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cell proliferation, has been shown to increase the susceptibility of human breast cancer cells to doxorubicin treatment ( de Luca et al. 2011 ). With regard to cancer development and treatment, a different role of GSH has been described in the
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cancer cells can favor tumor progression and resistance to therapy. Nonetheless, in the last years, HO-1 overexpression ha been demonstrated also in cells of the tumor microenvironment (TME) and proved to be involved in the gain of a tolerogenic phenotype
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Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain
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Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain
Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
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pathophysiology, and the therapeutic options based on mTOR regulation impact the progression of cancer, metabolic-associated diseases, and aging ( Zoncu et al. 2011 ). mTOR is a serine/threonine protein kinase belonging to the phosphoinositide 3-kinase (PI3K
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( Tsuboi et al. 2008 ). Moreover, increased levels of secreted DJ-1, for example, into serum, plasma, and cerebrospinal fluid have been observed in patients with sepsis ( Amatullah et al. 2017 ), breast cancer ( Tsuchiya et al. 2012 ), strokes
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Graphical Abstract
Abstract
Objective
Nonalcoholic steatohepatitis is a chronic liver disease caused by the progression of hepatocellular death and inflammation from simple steatosis. However, the pathogenesis of this disease remains unclear. Lipid peroxidation is one of the most critical factors in the development of nonalcoholic steatohepatitis; however, oxidised lipids – the products of lipid peroxidation – are insufficiently analysed. Here, we comprehensively analysed oxidised lipids in the liver during nonalcoholic steatohepatitis development in a choline-deficient, l-amino acid-defined, high-fat diet-fed mouse model.
Methods
Liver from C57BL/6J mice, fed a standard diet or a choline-deficient l-amino acid-defined high-fat diet for 1, 3, or 6 weeks, were collected to evaluate fibrosis, steatosis, inflammation, liver injury, and oxidised lipid production and to observe the suppression of these parameters upon vitamin E administration. In addition, organellar localisation of lipid peroxidation was assessed using fluorescence imaging. Finally, a mitochondria-targeted antioxidant was administered to model mice to investigate the mechanism underlying lipid peroxidation.
Results
We found an accumulation of oxidised triglycerides in the early stages of nonalcoholic steatohepatitis. Furthermore, our data indicate that oxidised triglycerides are generated by lipid peroxidation in lipid droplets due to mitochondria-derived reactive oxygen species.
Conclusion
These results suggest the importance of lipid droplet peroxidation in the progression of nonalcoholic steatohepatitis and may contribute to the development of therapeutic methods for nonalcoholic steatohepatitis in the future.
Significance statement
We demonstrate the specific and early occurrence of lipid peroxidation in nonalcoholic steatohepatitis pathogenesis and propose a previously unknown mechanism of disease progression.
PULSALYS SATT Lyon-Saint Etienne, Villeurbanne, France
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to oxidative stress which is related to cellular damage and aging process, and is implicated in the development of various diseases such as neurodegenerative disorders, chronic diseases and cancers ( Hayes et al. 2020 , Sharifi-Rad et al. 2020
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NBFC, National Biodiversity Future Center, Palermo, Italy
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Unità di Ricerca di Geriatria, Facoltà Dipartimentale di Medicina e Chirurgia. Università Campus Bio-Medico di Roma
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NBFC, National Biodiversity Future Center, Palermo, Italy
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as cardiovascular diseases, cancer, diabetes and neurodegenerative disease ( Kaeberlein 2013 ). In modern society, advanced healthcare can keep people alive longer, so the consequences of age and physiological decline become even more important to
Food4Future (F4F), c/o Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Grossbeeren, Germany
NutriAct Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany
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Food4Future (F4F), c/o Leibniz Institute of Vegetable and Ornamental Crops (IGZ), Grossbeeren, Germany
NutriAct Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal, Germany
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria
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to be found in human plasma in relevant amounts and thus have been studied in the context of different diseases including cancer, frailty, cataract, obesity, cardiovascular diseases and skin diseases ( Krinsky & Johnson 2005 , Thies et al. 2012
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acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported recently (see chapter 6), suggesting the importance of selenium in the protection against viral infection. In addition, the incidence of arteriosclerosis and cancer (e
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Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, KSA
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NRF2 expression ( Pomatto et al. 2018 , Fão et al. 2019 , Qu et al. 2020 ). Data on the effect of androgens on NRF2 remains disputed; work by Schultz et al. (2014) found that treating two types of cancer cell lines (LNCaP, C4-2B) with the
