Journal ArticleDOI
Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis
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TLDR
Although augmented concentrations of ROS and faulty antioxidant defense have been associated to NAFLD and related complications, mechanisms of action and proofs of principle should be highlighted to support the causative role of OxS and to translate its concept into the clinic.Abstract:
Significance: Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manif...read more
Citations
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Journal ArticleDOI
Mitochondrial electron transport chain, ROS generation and uncoupling (Review)
TL;DR: This review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS.
Journal ArticleDOI
Molecular pathways of nonalcoholic fatty liver disease development and progression
TL;DR: This review is aimed at integrating the overwhelming progress made in the characterization of the physiopathological mechanisms of NAFLD at a molecular level, to better understand the factor influencing the initiation and progression of the disease.
Journal ArticleDOI
Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?
TL;DR: This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation, and highlights the role of CD36/FAT fatty acid translocase inNAFLD pathogenesis.
Journal ArticleDOI
Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway.
Xiao-Juan Zhao,Han-Wen Yu,Yan-Zi Yang,Wen-Yuan Wu,Tian-Yu Chen,Ke-Ke Jia,Lin-Lin Kang,Rui-Qing Jiao,Ling-Dong Kong +8 more
TL;DR: Fructose-induced miR-200a low-expression increased Keap1 to block Nrf2 antioxidant pathway, and then enhanced ROS-driven TXNIP to activate NLRP3 inflammasome and disturb lipid metabolism-related proteins, causing inflammation and lipid deposition in BRL-3A cells is demonstrated.
Journal ArticleDOI
Therapeutic Landscape for NAFLD in 2020
TL;DR: The treatment landscape in this rapidly evolving field with an emphasis on drugs in Phase 2 and Phase 3 trials is reviewed, likely that patients develop the phenotype of NASH by multiple mechanisms and thus the optimal treatments ofNASH will likely evolve to personalized therapy once the authors understand the mechanistic underpinnings of NASh in each patient.
References
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Journal ArticleDOI
Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans
Silvie Timmers,Ellen Konings,L. Bilet,Riekelt H. Houtkooper,Tineke van de Weijer,Gijs H. Goossens,Joris Hoeks,Sophie E. van der Krieken,Dongryeol Ryu,Sander Kersten,Esther Moonen-Kornips,Matthijs K. C. Hesselink,Iris Kunz,Vera B. Schrauwen-Hinderling,Ellen E. Blaak,Johan Auwerx,Patrick Schrauwen +16 more
TL;DR: It is demonstrated that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction.
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Epidemiology of Non-Alcoholic Fatty Liver Disease
TL;DR: The majority of individuals with NAFLD do not develop NASH, and noninvasive markers such as the fatty liver index obtained from the Dionysos Study may be useful to screen forNAFLD in the general population.
Journal ArticleDOI
Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease
TL;DR: A greater fundamental understanding of the mechanisms that preserve protein folding homeostasis and redox status will provide new information toward the development of novel therapeutics for many human diseases.
Journal ArticleDOI
Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease
Zhiping Li,Shiqi Yang,Huizhi Lin,Jiawen Huang,Paul A. Watkins,Paul A. Watkins,Ann B. Moser,Ann B. Moser,Claudio DeSimone,Xiao Yu Song,Anna Mae Diehl +10 more
TL;DR: The concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD are supported and novel therapies for these common conditions are suggested.