Cardiorespiratory Fitness in Children with Overweight-Obesity: Insights into the Molecular Mechanisms
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE164873 | GEO | 2021/08/05
REPOSITORIES: GEO
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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: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
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:Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis (CH) of indeterminate potential (CHIP) involves expansion of mutated hematopoietic stem and progenitor cells (HSC/Ps) that leads to an increased risk of hematologic malignancy and cardiovascular disease (CVD). However, risk factors that contribute to CHIP-associated CH are poorly understood. A common, pro-inflammatory comorbidity responsible for enhancing the risk for developing type 2 diabetes mellitus (T2DM), CVD and cancer, obesity may exacerbate CHIP-associated diseases. We analyzed exome sequencing and clinical data from 47,466 individuals with valid CHIP in the UK Biobank. CHIP was present in 5.8% of the study population, and was associated with a significant increase in waist-to-hip ratio (WHR). The cancer genome atlas (TCGA) interrogation revealed that the mutation rate of CHIP is higher in patients with high BMI (>30 kg/m2) compared to those with low BMI (≤25 kg/m2) in six different cancer types. Utilizing mouse models of obesity bearing CHIP mutations, we show that both the compound mutant mice (Tet2-/-;Ob/Ob, Dnmt3a+/-;Ob/Ob) and CHIP mutant bone marrow (BM; Tet2-/-, Dnmt3a+/-, Asxl1+/- and Jak2+/-) transplanted into Ob/Ob mice develop rapid CH, leading to severe MPN/AML as well as CVD, which among other things, is associated with upregulation of intracellular calcium (Ca2+) levels and pro-inflammatory cytokines. Remarkably, calcium channel blocker nifedipine, in combination with metformin, MCC950 and anakinra, suppressed the growth of mutant CHIP cells, cardiovascular disease and restored normal hematopoiesis as well as serum Ca2+ and inflammatory cytokines. Thus, obesity is highly associated with the presence of CHIP and targeting CHIP mutant cells with a combination of metformin/nifedipine/MCC950/anakinra is a safe and inexpensive approach to treat CH and its associated abnormalities in obese individuals.
2022-01-08 | GSE193062 | GEO
Project description:Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.
2019-09-15 | GSE133526 | GEO
Project description:Cardiovascular disease (CVD) is exceedingly severe in patients with chronic kidney disease (CKD) and further aggravated by peritoneal dialysis (PD), exposing the patients to excessive amounts of intraperitoneal glucose. Children are devoid of pre-existing CVD and give insight into specific uremia and PD induced pathomechanisms. Fat surrounded omental arterioles beyond PD fluid penetration level were microdissected from uremic children at time of first PD catheter insertion (n=8), children on PD (n=5), and age and gender matched non-uremic children as controls (n=6). Adjacent sections of 4 arterioles per patient were used for transcriptomic analyses.
2018-04-12 | E-MTAB-5695 | biostudies-arrayexpress
Project description:Intensive lifestyle modification is believed to mediate cardiovascular disease (CVD) risk through traditional pathways that affect endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. Our study reveals that gene expression signatures are significantly modulated by rigorous lifestyle behaviors and track with CVD risk profiles over time. We examined the impact of a rigorous CVD risk reduction program on peripheral blood gene expression profiles in 63 participants and 63 matched controls to characterize molecular response to lifestyle modification and identify regulatory pathways important to cardiovascular health.
2014-02-24 | E-GEOD-46097 | biostudies-arrayexpress
Project description:Cardiovascular disease (CVD) is exceedingly severe in patients with chronic kidney disease (CKD) and further aggravated by peritoneal dialysis (PD), exposing the patients to excessive amounts of intraperitoneal glucose. Children are devoid of pre-existing CVD and give insight into specific uremia and PD induced pathomechanisms. Fat surrounded omental arterioles beyond PD fluid penetration level were microdissected from uremic children at time of first PD catheter insertion (n=8), children on PD (n=5), and age and gender matched non-uremic children as controls (n=6). Adjacent sections of 4 arterioles per patient were used for proteomic analyses.
2019-11-08 | PXD006298 | Pride
Project description:Fish contains high quality proteins and essential nutrients including vitamin D (VitD3). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors and studies showed an association between VitD3 deficiency, CVD and CVD risk factors such as diabetes. This study investigated acute effects of a single dose of VitD3, bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was done. Differences in whole-genome expression levels after vs. before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3+BPH treatments, respectively. VitD3-containing treatments affected the SLC25A20 gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.
2019-04-11 | GSE129604 | GEO
Project description:Viral infections are among the most common causes for fever without an apparent source (FWS) in young children; however, many febrile children are treated with antibiotics despite the absence of bacterial infection. Adenovirus, human herpesvirus 6 (HHV-6) and enterovirus are detected in children with FWS more often than other viral species. Virus and bacteria interact with pattern recognition receptors in circulating blood leukocytes and trigger specific host transcriptional programs that mediate immune response, and unique transcriptional signatures may be ascertained to discriminate between viral and bacterial causes for children with FWS. Microarray analyses were conducted on peripheral blood samples obtained from 51 pediatric patients with confirmed adenovirus, human herpesvirus 6 (HHV-6), enterovirus or bacterial infection. Whole blood transcriptional profiles could clearly distinguish febrile children from healthy controls, and febrile children with viral infections from afebrile children carrying the same virus. Molecular pathways regulating host immune response were the most affected in febrile children with infection. Pattern recognition programs were prominently activated in all febrile children with infection, while differential activation of transcriptional programs was observed among viral species. Interferon signaling pathway was uniquely activated in children with febrile viral infection, while a different set of pathways was uniquely activated in children with bacterial infection. Transcriptional signatures were identified and classified febrile children with viral or bacterial infection with 87% overall accuracy, an improvement from the current clinical practice of deducing from white blood cell (WBC) count status. Similar degree of accuracy was observed when we validated the signature probes on data sets from an independent study with different microarray platforms. The current study confirms the clinical utility of blood transcriptional analysis, suggests the composition of transcriptional signatures which can be used to ascertain the infectious etiology of febrile young children without an apparent source, thus limit the overuse of antibiotics on febrile children presenting with this common clinical complaint. Total RNA samples extracted from whole blood of young children were processed for hybridization onto Illumina Human-HT12 version 4 beadchips, and differential expression of the transcripts was analyzed between sick children with either viral or bacterial infection and healthy children.
2012-10-15 | E-GEOD-40396 | biostudies-arrayexpress