ESPE Abstracts (2014) 82 P-D-1-1-112

Mir-146a and -155 are Involved in FOXO1 Regulation and Non Alcoholic Fatty Liver Disease in Childhood Obesity

Luisa Montaninia, Pietro Lazzeronia, Chiara Sartoria, Valerio Nobilib, Pellegrino Crafaa, Sergio Bernasconia & Maria E Streeta

aUniversity Hospital of Parma, Parma, Italy; bBambino Gesù Children’s Hospital, IRCCS, Rome, Italy

Background: Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in childhood, in obese subjects and associated with insulin resistance.FOXO1 is a key regulator in insulin signalling and in intracellular adipogenesis, and is implicated in liver steatosis. We have previously identified that a group of miRNAs are involved in its epigenetic regulation.

Objective and hypotheses: We aimed to assess in liver tissue and in serum whether two of these miRNAs were differentially expressed and showed relationships with NAFLD.

Method: MiR-146a and -55 were extracted from paraffin embedded liver biopsies, quantified by TaqMan microRNA assays and normalized with respect to RNU48 in ten young subjects having NAFLD, and from normal liver tissue of comparable subjects. Both were overexpressed in NAFLD. We enrolled obese children with (11.89±0.86 years; BMI–SDS: 3.41 ; 8M, 8F), and without liver steatosis at ultrasound (11.81±1.0 years; BMI–SDS: 3.15; 5 M, 4F). Pubertal stages were similar. The HOMA-IR index, the waist circumferences (Wtc), and the waist to height ratios (Wt/Ht) were significantly higher in the subjects with NAFLD. miRNA-146a and -155, purified from serum were quantified by TaqMan microRNA assays and normalized with respect to miR-16, and -93, as housekeeping miRNAs. dCts were normalized with respect to an appropriate pool of dCt controls of comparable age, sex, and pubertal stage (N.11 pubertal stage 1 and N.12 pubertal stages 3–5) and expressed as fold change (Log10).

Results: Both miR-146a and -155 (0.85±0.59 vs −1.15±1.74, P<0.05) were increased in the obese children having NAFLD. In the entire group, miR-146a was correlated with Wtc (R: 0.65; P: 0.01) and with Wt/Ht (R: 0.52; P: 0.05), and miR-155 with BMI–SDS (R: 0.55; P: 0.04), Wtc (R: 0.71; P: 0.004), and Wt/Ht (R: 0.64; P: 0.01). MiR-146a and -155 were also correlated (R: 0.47; P: 0.04).

Conclusion: Both miR-146a and -155 were over-expressed in NAFLD both in tissue and in serum and showed relationships with adipose fat distribution. Both have been previously described in tumours and inflammation, besides insulin-insensitivity by us, recently. Obesity is a chronic inflammatory disease and the prevalence of tumours is increased. Further investigation is ongoing to verify whether these miRNAs could become markers of disease.

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