Clinical implications of understanding the association between oxidative stress and pediatric NAFLD.
Oxidative stress is central to the pathogenesis of non-alcoholic steatohepatitis. The reactive oxygen species (ROS) that characterise oxidative stress are generated in several cellular sites and their production is influence by multi-organ interactions. Areas covered: Mitochondrial dysfunction is the main source of ROS in fatty liver and is closely related to endoplasmic reticulum stress. Both are caused by lipotoxicity and together these three factors form a cycle of progressive organelle damage, resulting in sterile inflammation and apoptosis. Adipose tissue inflammation and intestinal dysbiosis provide substrates for ROS formation and trigger immune activation. Obstructive sleep apnea and abnormal divalent metal metabolism may also play a role. Expert commentary: The majority of available high-quality data originates from studies in adults and there are fewer therapeutic trials performed in pediatric cohorts, therefore conclusions are generalised to children. Establishing the role of organelle interactions, and its relationship with oxidative stress in steatohepatitis, is a rapidly evolving area of research.
a Metabolic Research Laboratories, Institute of Metabolic Science , University of Cambridge , Cambridge , UK.|b Department of paediatrics , University of Cambridge , Cambridge , UK.
Jake P
JP
Mann
c Medical Directorate , Bambino Gesu Hospital - IRCCS , Rome , Italy.
Massimiliano
M
Raponi
d Hepatometabolic Unit , Bambino Gesu Hospital - IRCCS , Rome , Italy.|e Liver Research Unit , Bambino Gesu Hospital - IRCCS , Rome , Italy.
Valerio
V
Nobili
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D004734:Energy Metabolism; D000069196:Gastrointestinal Microbiome; D020022:Genetic Predisposition to Disease; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications
D017382:Reactive Oxygen Species
NAFLD; lipotoxicity; mitochondrial dysfunction; oxidative stress; pediatric; steatohepatitis