FTO and PLAG1 Genes Expression and FTO Methylation Predict Changes in Circulating Levels of Adipokines and Gastrointestinal Peptides in Children

Abstract

Adipokines and gastrointestinal tract hormones are important metabolic parameters, and both epigenetic factors and differential gene expression patterns may be associated with the alterations in their concentrations in children. The function of the FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) in the regulation of the global metabolic rate is well described, whereas the influence of protooncogene PLAG1 (PLAG1 zinc finger) is still not fully understood. A cross-sectional study on a group of 26 children with various BMI values (15.3–41.7; median 28) was carried out. The aim was to evaluate the dependencies between the level of methylation and expression of aforementioned genes with the concentration of selected gastrointestinal tract hormones and adipokines in children. Expression and methylation were measured in peripheral blood mononuclear DNA by a microarray technique and a restriction enzyme method, respectively. All peptide concentrations were determined using the enzyme immunoassay method. The expression level of both FTO and PLAG1 genes was statistically significantly related to the concentration of adipokines: negatively for apelin and leptin receptor, and positively for leptin. Furthermore, both FTO methylation and expression negatively correlated with the concentration of resistin and visfatin. Cholecystokinin was negatively correlated, whereas fibroblast growth factor 21 positively correlated with methylation and expression of the FTO gene, while FTO and PLAG1 expression was negatively associated with the level of cholecystokinin and glucagon-like peptide-1. The PLAG1 gene expression predicts an increase in leptin and decrease in ghrelin levels. Our results indicate that the FTO gene correlates with the concentration of hormones produced by the adipose tissue and gastrointestinal tract, and PLAG1 gene may be involved in adiposity pathogenesis. However, the exact molecular mechanisms still need to be clarified.

Prognostic Observational Analysis of BMI, Leptin, and Adiponectin in Children With Acute Lymphocytic Leukemia Undergoing Remission-Induction Chemotherapy

“…Detection of MRD during remission induction and consolidation therapy is the most sensitive method to evaluate treatment response and one of the strongest predictors of outcome in childhood acute lymphoblastic leukemia. Several studies have demonstrated the prognostic significance of measuring MRD in childhood ALL, suggesting that MRD positivity at serial time points during the treatment is highly predictive of relapse, and associated with poor treatment outcome ( 29 , 30 ). A recent study suggested that MRD levels at the end of remission induction therapy measured using multiparameter flow cytometry have clinical significance in childhood ALL.…”

What Is the Relationship Between Body Mass Index, Sex Hormones, Leptin, and Irisin in Children and Adolescents? A Path Analysis

“…The path association may be related to genetic and epigenetic factors. Studies reported that the expression level of fat mass and obesity associated gene (FTO) and pleomorphic adenoma gene 1 (PLAG1) genes associated with obesity was significantly related to the concentration of leptin (55,56).…”

Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children

“…Another additional explanation for our results may be related to the fact that epigenetic factors and differential gene expression patterns are associated with variations in the concentrations of leptin ( 17 ). In fact, in a recent publication, a different expression level of the FTO gene, extensively described as linked to obesity, has been related to the concentration of hormones produced by the adipose tissue, being positively correlated with leptin ( 18 ). Moreover, higher FTO expression has been associated with an increase of the concentration of FFA, suggesting that the FTO gene may play a role in the development of the impairment of glucose-lipid metabolism related to obesity in children ( 19 ).…”