Search

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. [ABSTRACT FROM AUTHOR]

Simple Summary: The increasing frequency of hematopoietic stem cell transplantation (HSCT) and average postprocedural survival time has improved the knowledge about long-term adverse effects of transplantation in adulthood; i.e., an increase in the incidence of systemic diseases, like cardiovascular diseases or metabolic syndromes, as well as various types of endocrine disorders. A screening test identifying children at high risk of metabolic complications of HSCT might be useful in this group of patients. The aim of our study was to investigate the microarray-determined expression of genes with known functions related to lipid metabolism and their correlation with laboratory and clinical parameters. The next phases of research should include preemptive management of lipid abnormalities based on the results of microarray analysis. This might be the basis of personalized therapy of lipid disorders in patients with dyslipidemia or abnormalities or key metabolic hormones, both before and after HSCT. Metabolic disorders in children after hematopoietic stem cell transplantation (HSCT) are poorly characterized. However, it is known that dyslipidemia and insulin resistance are particularly common in these patients. We conducted a prospective study of 27 patients treated with HSCT to assess the possibility of predicting these abnormalities. We measured gene expressions using a microarray technique to identify differences in expression of genes associated with lipid metabolism before and after HSCT. In patients treated with HSCT, total cholesterol levels were significantly higher after the procedure compared with the values before HSCT. Microarray analysis revealed statistically significant differences in expressions of three genes, DPP4, PLAG1, and SCD, after applying the Benjamini–Hochberg procedure (pBH < 0.05). In multiple logistic regression, the increase of DPP4 gene expression before HCST (as well as its change between pre- and post-HSCT status) was associated with dyslipidemia. In children treated with HSCT, the burden of lipid disorders in short-term follow-up seems to be lower than before the procedure. The expression pattern of DPP4 is linked with dyslipidemia after the transplantation. [ABSTRACT FROM AUTHOR]

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism. [ABSTRACT FROM AUTHOR]