Background: MicroRNAs (miRNA) are small non coding RNA molecules, key regulators of metabolic pathways. Obesity is characterised by many metabolic changes. NAFLD is seen as a complication of obesity. FOXO-1, key regulator in insulin signalling, has been shown to be implicated in NAFLD. We previously identified miRNAs regulators of the FOXO-1 gene.
Objective and hypotheses: To assess in serum whether the regulation of miR-146a and miR-486-5p, FOXO1 gene regulators, changed in obese subjects, and whether any changes were related with measurements of adipoity and indexes of insulin sensitivity. Relationships with NAFLD were investigated also.
Method: 83 obese children were consecutively enrolled (CA: 11.35±0.33 years-range: 3.7816.83 years; BMISDS: 3.17±0.10; males: 40; females: 43) with (N: 37) and without (N: 46) NAFLD. A group of 23 healthy controls comparable for age, sex and pubertal stage (CA: 12.1±1.3 years; BMISDS: 0.56±0.66; males: 12; females: 11) was used for comparison. NAFLD was diagnosed by liver ultrasound. Total RNA from serum was extracted using the MirVana PARIS kit. MiRNAs were quantified by TaqMan microRNA Assays and normalized with respect to miR-16 and miR-93, as housekeeping miRNAs. dCts were normalized with respect to the pool of dCt controls. Relative gene expression was then presented as fold change (Log10).
Results: Obese subjects having NAFLD had a larger waist circumference(96.63±2.58 cm vs 88.58±1.87 cm, P<0.05). MiR146a and 486-5p were similar in females and males. In the obese children, miR146a was downregulated (−2.06±0.05) and miR486-5p upregulated (0.56±0.11) compared with controls. No significant difference was detected based on the presence of NAFLD. MiR-146a was correlated with BMISDS (P=0.013; R=−0.3), with waist circumference (P=0.006; R=0.35), and with the HOMA-IR index (P=0.015; R=0.3).
Conclusion: Specific circulating miRNAs show changes in obesity and miR-146a shows clear relationships with BMI, distribution of adiposity and parameters of insulin sensitivity.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology