Circulating microRNAs are deregulated in overweight/obese children: preliminary results of the I.Family study

Abstract

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs involved in the modulation of gene expression and in the control of numerous cell functions. Alterations of miRNA patterns frequently occur in cancer and metabolic disorders, including obesity. Recent studies showed remarkable stability of miRNAs in both plasma and serum making them suitable as potential circulating biomarkers for a variety of diseases and conditions.The aim of this study was to assess the profile of circulating miRNAs expressed in plasma samples of overweight or obese (OW/Ob) and normal weight (NW) prepubertal children from a European cohort (www.ifamilystudy.eu). The project, aimed to assess the determinants of eating behavior in children and adolescents of eight European countries, is built on the IDEFICS cohort (www.ideficsstudy.eu), established in 2006. Among the participants of the I.Family Italian Cohort, ten OW/Ob (age 10.7 ± 1.5 years, BMI 31.6 ± 4.3 kg/m2) and ten NW (age 10.5 ± 2.7 years, BMI 16.4 ± 1.7 kg/m2) children were selected for the study. Gene arrays were employed to differentially screen the expression of 372 miRNAs in pooled plasma samples. Deregulated miRNAs (p < 0.05) were further validated in the individual samples using a real-time PCR (RT-qPCR) approach.ResultsUsing a significance threshold of p < 0.05 and a fold-change threshold of ± 4.0, we preliminarily identified in the pooled samples eight miRNAs that differed between the OW/Ob and NW groups. The validation by RT-qPCR in the individual plasma samples showed a twofold upregulation of miR-31-5p, a threefold upregulation of miR-2355-5p, and a 0.5-fold downregulation of miR-206 in OW/Ob as compared with NW. The molecular functions of these differentially expressed plasma miRNAs as well as their expected mRNA targets were predicted by bioinformatics tools.ConclusionsThis pilot study shows that three circulating miRNAs are differentially regulated in OW/Ob as compared with NW children. Although causal pathways cannot be firmly inferred by these results, that deserve confirmation in larger samples, it is conceivable that circulating miRNAs may be novel biomarkers of obesity and related metabolic disturbances.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0525-3) contains supplementary material, which is available to authorized users.

Changes in adipose tissue cellular composition during obesity and aging as a cause of metabolic dysregulation

“…Several miRNAs have been identified in regulating progenitor cells or preadipocytes found in the SVF to adipocytes (Fei et al, 2013; Iacomino et al, 2016). It has been made clear that miRNA play a role in adipogenesis regulation, and evidence shows that dysregulation of miRNA expression is causative or indicative of disease states (Iacomino et al, 2016; Villageois et al, 2011).…”

“…Several miRNAs have been identified in regulating progenitor cells or preadipocytes found in the SVF to adipocytes (Fei et al, 2013; Iacomino et al, 2016). It has been made clear that miRNA play a role in adipogenesis regulation, and evidence shows that dysregulation of miRNA expression is causative or indicative of disease states (Iacomino et al, 2016; Villageois et al, 2011). Several miRNAs, specifically miR-143, have been identified to regulate the ERK5-PPARγ pathway during preadipocyte differentiation, and that this dysregulation promotes adipogenesis and obesity with increased age (Fei et al, 2013).…”

“…Several miRNAs, specifically miR-143, have been identified to regulate the ERK5-PPARγ pathway during preadipocyte differentiation, and that this dysregulation promotes adipogenesis and obesity with increased age (Fei et al, 2013). Another preliminary study identified circulating miRNAs miR-31-5p, miR-2355-5p and miR-206 as potentially associated with early obesity (Iacomino et al, 2016). They defined early obesity as childhood obesity and compared overweight samples to normal weight samples and identified three main circulating miRNAs that were differentially expressed (Iacomino et al, 2016).…”

“…Another preliminary study identified circulating miRNAs miR-31-5p, miR-2355-5p and miR-206 as potentially associated with early obesity (Iacomino et al, 2016). They defined early obesity as childhood obesity and compared overweight samples to normal weight samples and identified three main circulating miRNAs that were differentially expressed (Iacomino et al, 2016). The study focused on preadipocyte differentiation, indicating that miRNAs are altered by obesity most likely affecting progenitor cells differentiation or self-renewal.…”

miRNAs in nutrition, obesity, and cancer: The biology of miRNAs in metabolic disorders and its relationship with cancer development

“…Lower expression of omental miR‐132 was correlated with higher macrophage infiltration, whereas higher expression of miR‐181a was associated with lower circulating adiponectin levels . A pilot study showed that three circulating miRNAs (miR31‐5p, miR‐2355‐5p and miR‐206) are differentially regulated in overweight or obese children compared with those with normal weight .…”