Exosomal miRNAs Profile in Children’s Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid

Abstract

Objective: The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD. Methods: Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation analysis was used to investigate the association between DEM and clinical parameters. Results: Eighty-two miRNAs were differentially expressed (absolute fold change > 2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41-0.59), alanine aminotransferase (r, 0.36-0.52), aspartate transaminase (r, 0.31-0.48) and uric acid (UA, r, 0.51-0.69; p < 0.05). Conclusions: Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.

Clinical spectrum transition and prediction model of nonalcoholic fatty liver disease in children with obesity

“…However, the sensitivity of ultrasound for the detection of mild steatosis is 60.9%-65% ( 18 , 19 ). Thus, alternative noninvasive strategies, such as serum biomarkers (ALT/AST ratio, APR Index, BARD score, NAFLD fibrosis score, FIB-4 index, exosomal miRNAs), and imaging techniques (elastography) have made great strides over the past decade ( 20 , 21 ). Other cardiometabolic risk factors, such as triglyceride glucose-waist circumference(TyG-WC), triglyceride glucose-body mass index(TyG-BMI), triglyceride glucose-waist-to-height ratio(TyG-WHtR), waist-to-hip ratio(WHR), waist-to-height ratio(WHtR), and homeostatic model assessment of insulin resistance(HOMA-IR) have also been reported to be suitable predictors of NAFLD ( 22 – 24 ).…”

Circulating microRNAs Are Associated With Metabolic Markers in Adolescents With Hepatosteatosis

“…( 30 ) demonstrated decreased liver and serum miR-155 levels in adult patients with NAFLD, Zhou et al. ( 31 ) showed increased serum levels in children with NAFLD. In the current study, we found positive correlations between serum miR-155 level and insulin and adiponectin concentrations in children with IR regardless of NAFLD status, and IHTG and liver enzymes in children with NAFLD only.…”

Insulin resistance and insulin sensitizing agents

“…MicroRNA-122 is associated with IR, inflammation and adiposity in overweight adults and regulates insulin signaling pathways, as revealed by functional analysis [58]. Moreover, the exosomal microRNA profile correlates with BMI, transaminases and uric acid in children with non-alcoholic fatty liver disease (NAFLD) [59] and differs between healthy and BMI-matched T2DM humans, who display higher levels of microRNA-20b-5p, which modulates the Akt signaling when transfected in SkM cells [60]. People with T2DM display also upregulation of microRNA-144 and downregulation of its predicted target IRS1, which supports the relevance of microRNA-144 for T2DM development [61].…”