Nonalcoholic fatty liver disease (NAFLD),which represents the leading cause of hepatic damage worldwide,is modulated by epigenetic factors, in particular microRNAs (miRNAs), which control at post-transcriptional level many complementary target mRNA. However, the evidence for this is inconsistent. The high stability and expression of circulating exosomal miRNAs may allow their use as candidate biomarkers. For the discovery phase,exosomes were isolated from the serum of patients with obesity as the controls (n=5) and obesity&NAFLD (n=5) for microarray analysis of miRNAs. Thirty miRNAs were expressed significantly higher (>1.5-fold) in patients with obesity&NAFLD, but not in patients with obesity. Notably, expression of 5 miRNAs (miRNA-122-5p, -3591-3p, -1290, -23a-5p,and let-7g-3p) was elevated by more than 4.5-fold in patients with obesity&NAFLD. For the validation phase,miRNAs were analyzed using quantitative RT-PCR analysis in exosomes from the serum of patients with obesity control (n=20) and patients with obesity&NAFLD (n=20). These miRNAs and their target genes may regulate a wide spectrum of biological processes and metabolic homeostasis,including lipid synthesis, fatty acids and glucose catabolism, inflammation, proliferation, apoptosis and necrosis, which have been known to be epigenetically deregulated in NAFLD. These findings suggest that serum exosomal miRNAs might be used as novel biomarkers to reflect the progression of NAFLD.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology