Abstract
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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a generic term that describes a spectrum of diseases including non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), fibrosis, and NAFLD-cirrhosis [1]
LPS infiltration leads to pro-inflammatory cytokine production and liver Kupffer cell (KC) activation, which can lead to the activation of hepatic stellate cells and fibrosis [123]
We focus here on a few miRNAs with evidence to support their regulatory roles in the lipogenic, gluconeogenic, or β-oxidation pathways at the nexus of NAFLD development and progression (Figure 1)
Summary
Non-alcoholic fatty liver disease (NAFLD) is a generic term that describes a spectrum of diseases including non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), fibrosis, and NAFLD-cirrhosis [1]. The global epidemic of NAFLD is increasing exponentially owing to the growing prevalence of obesity and type 2 diabetes (T2D) in children and adults along with the aging population [2]. NAFLD is estimated to affect 34% of obese children aged 2–19 years and 10% of the general pediatric population [5]. NAFLD has been renamed by some as metabolic (dysfunction) associated fatty liver disease (MAFLD). Pediatric NAFLD has a complex pathophysiology and is different from adult NAFLD with multiple inputs, including perinatal events. Understanding these differences may lead to new biomarkers and opportunities for novel therapeutics
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