Circulating microRNAs associated with C-type natriuretic peptide in childhood obesity

Abstract

Circulating microRNAs (miRNAs) are potential biomarkers of metabolic disease implicated in the pathogenesis of obesity and at present, no data are available on a possible contribution of C-type natriuretic peptides (CNP)-linked miRNAs to childhood obesity. Our aims were to 1) perform an in silico-analysis to identify miRNAs targeting CNP gene; 2) recognize CNP-linked miRNAs associated with obesity; 3) characterize their circulating profiling in normal-weight (N) and obese adolescents (O). A clinical examination was performed in 25 N and 52 O adolescents. CNP plasma levels were detected by immunometric assay while miRNA expression was carried out on peripheral blood using Real-Time PCR. Plasma CNP resulted significantly lower in O than in N (5.58 ± 0.62 vs.14.78 ± 1.35 pg/mL, p < 0.0001). In silico-analysis disclosed several specific circulating CNP-linked miRNAs among which miR-33a-3p, miR-223−5p and miR-142−5p also associated with obesity. MiR-199−5p and miR-4454, known to be associated with obesity but not with CNP, were also studied. miR-223−5p and miR-33a-3p resulted significantly (p = 0.05) higher in O (0.97 ± 0.1; 0.85 ± 0.1, respectively) than in N (0.66 ± 0.11; 0.51 ± 0.08, respectively). Plasma CNP correlated inversely with miR-33a-3p (p = 0.036), miR-223−5p (p = 0.004), miR-199−5p (p = 0.003) and miR-4454 (p < 0.0001). Significantly positive correlations were observed between miR-33a-3p and miR-223−5p (p = 0.002) and between miR-199−5p and miR-4454 (p = 0.0001). Applying a multiple linear regression model, miR-142−5p, miR-199a-5p, miR-223−5p, miR33a-3p, diastolic blood pressure (DBP) and age were independent determinants of CNP. Our results underline the concept that expanding our knowledge on the behaviour of circulating miRNA profile may have a promising role for early identification of obese children at increased risk of cardiometabolic alterations.