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Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

1
Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3
Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(10), 3166; https://doi.org/10.3390/nu12103166
Received: 10 September 2020 / Revised: 12 October 2020 / Accepted: 13 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Nutrition and Metabolic (Non-alcoholic) Fatty Liver Disease (NAFLD))
Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions. View Full-Text
Keywords: pediatric NAFLD; clinical biomarkers; microRNAs; developmental programming; microbial dysbiosis; trained immunity pediatric NAFLD; clinical biomarkers; microRNAs; developmental programming; microbial dysbiosis; trained immunity
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Mandala, A.; Janssen, R.C.; Palle, S.; Short, K.R.; Friedman, J.E. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients 2020, 12, 3166.

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