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.
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.
Project description:Distinct whole blood transcriptome profile of children with metabolic healthy overweight/obesity compared to metabolic unhealthy overweight/obesity
Project description:Background: An important feature to vitamin D physiology is its gender dependence. The aim of this study was to examine whether vitamin D exerts a sexually dimorphic effect on the blood coagulation pathway among adults with overweight. Methods: This study compared the serum proteomic profiles of age and BMI-matched males (n=26) and pre-menopausal females (n=24) with overweight that attained vitamin D sufficiency after a 12-month intervention. Unprocessed serum was subjected to depletion-free, quantitative proteomic analysis using our previously published methodology. Results. A total of 1,841 proteins were profiled (p < 0.05). The analysed proteins vitamin-K dependent protein C, von Willebrand factor, fibrinogen gamma chain and multimerin-1 were ELISA validated to be differentially affected between genders by vitamin D status improvement. Conclusions: Vitamin D optimization exhibits a sexually dimorphic effect on the blood coagulation pathway among adults with overweight. This gender specific vitamin D effect should be taken into consideration in the design and interpretation of vitamin D observational and intervention studies.
Project description:<p>While the risk factors for Type 2 diabetes (T2DM) are known, early predictive markers of transition from normal to a prediabetes state are unidentified. We studied the basal metabolism and metabolic response to a mixed-meal challenge in 110 healthy subjects in the age group of 18 to 40 years (Male:Female = 1:1); grouped into first degree relatives of patients with T2DM (n = 30), those with a body mass index >23 kg/m2 but <30 kg/m2 (n = 30), those with prediabetes (n = 20) and normal controls (n = 30). We performed an untargeted metabolomics analysis of plasma and related that with clinical and biochemical parameters, markers of inflammation, and insulin sensitivity. Similar to prediabetes subjects, overweight subjects had insulin resistance and significantly elevated levels of C-peptide, adiponectin and glucagon and lower level of ghrelin. Metabolites such as MG(22:2(13Z, 16Z)/0:0/0:0) and LysoPC (15:0) were reduced in overweight and prediabetes subjects. Insulin sensitivity was significantly lower in men. Fasting levels of uric acid, xanthine, and glycochenodeoxycholic-3-glucuronide were elevated in men. However, both lysophospholipids and antioxidant defense metabolites were higher in women. Impaired postprandial metabolism and insulin sensitivity in overweight normoglycemic young adults indicates a risk of developing hyperglycemia. Our results also indicate a higher risk of diabetes in young men.</p>
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.
Project description:We aimed at identification of variations of genome expression in white blood cells, which could serve as blood markers of early dementia in adults with Down syndrome
Project description:Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of tumors for which the patients’ body mass index (BMI) was ascertained. Sample profiles were stratified according to patients’ obesity phenotype defined as normal (BMI <25), overweight (BMI 25-29.9), or obese (BMI>30). Widespread alterations in gene expression were evident in breast tumors from obese patients as compared to tumors from other patients, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. Keywords: two group comparison Primary breast tumor specimens were obtained from patients. Study volunteers completed questionnaires used to define historically normal (BMI<=24.9), overweight (BMI 25-29.9), or obese (BMI>=30) patient categories according to established WHO criteria.