Distinct whole blood transcriptome profile of children with metabolic healthy overweight/obesity compared to metabolic unhealthy overweight/obesity
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PROVIDER: PRJNA612214 | ENA |
REPOSITORIES: ENA
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Project description:Background and aims: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes (e.g. fasting glucose, serum triglycerides, etc.). The underling mechanisms for those differences are still unclear. This study aimed to analyze the whole blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF) and, vascular endothelial growth factor A (VEGF) were additionally determined. Total-blood RNA was analyzed by 5’-end RNA sequencing. Two different bioinformatics approaches were performed: 1) Differential gene expression analyses using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status) and 2) weighted gene coexpression network analyses (WGCNA). Results: Children with MHO had lower values of pro-inflammatory cytokines TNF-α and IL-6 compared to MUO (p < 0.05). 40 genes were differentially expressed (FDR < 0.05) in children with MHO compared to MUO. WGCNA analysis identified 23 gene coexpression modules (i.e. clusters of genes) with low preservation (Zsummary < 2) in children with MHO compared to MUO. Differential and WGCNA gene expression patterns identified 32 genes linked to metabolism, mitochondrial and immune functions. Conclusions: Whole blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. The identified gene expression patterns related to metabolism, mitochondrial and immune functions can promote a better understanding of cardiovascular disease prognosis in individuals with MHO.
2020-11-05 | GSE146869 | GEO
Project description:This study aimed to analyze the whole-blood transcriptome profile of fit children with overweight/obesity (OW/OB) compared to unfit children with OW/OB. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were evaluated. VO2peak was assessed using a gas analyzer, and participants were categorized into fit or unfit according to the CVD risk-related cut-points. Whole-blood transcriptome profile (RNA sequencing) was analyzed. Differential gene expression analysis was performed using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status). Results: 256 genes were differentially expressed in fit children with OW/OB compared to unfit children with OW/OB after adjusting by sex and maturational status (FDR < 0.05). Enriched pathways analysis identified gene pathways related to inflammation (e.g., dopaminergic and GABAergic synapse pathways). Conclusion: The distinct pattern of whole-blood gene expression in fit children with OW/OB reveals genes and gene pathways that might play a role in reducing CVD risk factors later in life.
2021-08-05 | GSE164873 | GEO
Project description:Background: The current knowledge about the molecular mechanisms underlying the health benefits of exercise is still limited, especially in the pediatric population. We set out to investigate the effect of a 20-week exercise intervention on whole blood transcriptome profile (RNA-seq) in children with overweight/obesity. Methods: Twenty-four pre-pubertal children (10.21 ± 1.33 years, 46% girls) with overweight/obesity, were randomized to either a 20-week exercise program (intervention group; n=10), or to a non-exercise control group (usual lifestyle, n=14). Whole blood transcriptome profile was analysed using RNA-seq STRT2 technique. Gene expression analysis was carried out with the Limma R/Bioconductor software package, and the gene ontology (GO) and pathway enrichment analyses were performed using R. Ingenuity Pathway Analysis (IPA) was performed for gene network detection. The transcriptome data were in silico validated using PHENOPEDIA and meta-analysis database extrameta.org. Results: 161 genes were differentially expressed between the exercise and the control groups among boys, and 121 genes among girls (p-value < 0.05), while after multiple correction, no significant difference between groups persisted in gene expression profiles (FDR > 0.05). Based on non-corrected analyses, the enriched GO processes and molecular pathways highlighted the effect of exercise on different immune response related pathways in boys (antigen processing and presentation, infections, and T cell receptor complex) and girls (Fc epsilon RI signaling pathway) (FDR < 0.05). In silico data mining and validation analyses (using PHENOPEDIA and meta-analysis database extrameta.org) highlight top genes regulated by exercise such as CD6, HLA-C, TNFRSF1A, MYD88, and NFKBIA genes in boys and RAC1, ANXA6, FYN, INPP5D, PIK3CD and SPARC genes in girls. Conclusion: These results suggest that 20-week exercise program influences different immune processes in children with overweight/obesity. The transcriptome differences between boys and girls could partly be explained, in addition to the gender differences, by the distinct intensity in the exercise intervention as boys had stronger exercise stimulus in training. Our findings should be considered exploratory and preliminary given the relatively small sample size. Larger and more powered randomized controlled trials should confirm or contrast our findings.
2023-09-19 | GSE193771 | GEO
Project description:Cardiorespiratory Fitness in Children with Overweight-Obesity: Insights into the Molecular Mechanisms
| PRJNA692240 | ENA
Project description:In the past few decades, the prevalence of overweight and obesity has sharply increased in children and adolescents. Childhood obesity life are associated with increased risk of cardiovascular disease (CVD), diabetes mellitus, metabolic syndrome, sleep disturbances and certain cancers in adulthood. Childhood obesity has become a serious global public health challenge. Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. We used microarrays to detail the differential expression profile of lncRNAs and mRNAs in obese children compared with non-obese children.
2018-06-14 | GSE104815 | GEO
Project description:In order to explore the effect of hypertension and overweight/obesity on human visceral adipose tissue transcriptome, we collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.
2023-07-03 | GSE217007 | GEO
Project description:In this project, the effects of a 20-week exercise intervention on whole blood genome-wide DNA methylation signatures (CpG sites level) in boys and girls with overweight/obesity (OW/OB) were investigated. Twenty-three children (10.05 ± 1.39 years, 56% girls) with OW/OB, were randomized to either a 20-week exercise intervention (exercise group [EG]; n=10; 4 boys/ 6 girls), or to usual lifestyle (control group [CG] (n=13; 6 boys/ 7 girls). Whole blood genome-wide DNA methylation and transcriptome profile (RNA-seq) analyses were performed before and after the intervention period. Changes in the DNA methylation sites of 485 and 386 CpGs were induced by the exercise intervention (compared to the control group) in boys and girls respectively (p < 0.001). These CpG sites mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function in boys or girls (p < 0.05). In boys, changes on the DNA methylation status of 87 CpG sites (from the subset of 485 significant CpGs) associated with changes in the gene expression levels of 51 gene transcripts which were regulated by exercise (p < 0.05). Among girls, changes on DNA methylation at 46 CpG sites (from the initial 386 significant CpGs) were associated with changes in the gene expression levels of 30 gene transcripts affected by exercise. Gene transcripts affected by exercise-induced DNA methylation were related to obesity, metabolic syndrome, and inflammation. Nevertheless, none of the presented analyses survived multiple testing correction (FDR > 0.05). This multi-omics approach reveals that exercise may regulate gene pathways involved in metabolism and immune functions in blood cells of boys and girls with OW/OB. These preliminary results provide an important first step to characterize the molecular response to exercise interventions in pediatric populations.
2022-07-07 | GSE193730 | GEO
Project description:Analysis of rectus femoris samples from chidren with obesity and normal weight. Obese children display insulin resistance (IR) and other metabolic abnormalities at higher rates than do normal weight children. Results provide insight into the molecular mechanisms underlying the pathogenesis of childhood obesity.
2022-01-31 | GSE139400 | GEO
Project description:Effects of 20-week exercise on whole-blood genome-wide DNA methylation profile in children with overweight/obesity
| PRJNA797430 | ENA
Project description:Pediatric obesity prevalence is rapidly rising worldwide and “omic” approaches are helpful in obesity molecular pathophysiology investigation. This work aimed at the identification of transcriptional differences in subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB) or severe obesity (SV) respect those with normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. Considering BMI z-score, chil-dren were stratified into 4 groups: SV, OB, OW, NW. scAT RNA-Seq analyses were performed, differential expression analysis was achieved using the DESeq2 R package. Pathways analysis was performed to gain biological insights on gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared to NW, OW, and OB. KEGG pathway analysis showed involvement for coding transcripts mainly in li-pid metabolism. GSEA analysis revealed upregulation of lipid degradation and metabolism in SV vs OB and SV vs OW. Bioenergetic processes and the catabolism of branched-chain amino acids resulted upregulated in SV when compared to OB, OW, NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in periumbilical scAT of children with severe obesity with respect to normal weight, overweight or mild obesity.
2023-05-03 | GSE228892 | GEO