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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...

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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.

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

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

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.
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