ABSTRACT: The aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children. PBMCs were obtained from 12 overweight/obese boys for RNA extraction and hybridization on Affymetrix microarrays. We performed the microarray analysis at baseline and after a weight loss intervention program in a total of 24 samples. They were distributed by dietary response as high and low responders.
Project description:The aim of this study was to analyze gene response to a 10-week dietary intervention for weight loss in peripheral blood mononuclear cells of overweight/obese male children.
Project description:The nutritional intervention program “DiOGenes” focuses on how obesity can be prevented and treated from a dietary perspective. We have generated differential plasma proteome profiles in the DiOGenes cohort to identify proteins associated with weight loss and maintenance and explore their relation to body mass index, fat mass, insulin resistance and sensitivity. Relative protein quantification was obtained at baseline and after combined weight loss/maintenance phases using isobaric tagging and MS/MS. 473 subjects were measured at baseline and end of the intervention; 183 proteins were quantified in more than 70% of the plasma samples. The MS-based proteomic analysis of this large cohort of non-diabetic overweight and obese individuals concomitantly identified known and novel proteins associated with weight loss and maintenance. ClinicalTrials.gov Identifier: NCT00390637
Project description:Subcutaneous adipose tissue transcriptomes were compared between 21 obese individuals that either maintained weight loss (good controllers) or regained weight (poor controllers) during a 2-phase dietary Intervention. Dietary intervention: Individuals underwent 8-weeks of calorie-restriction, then 6-months of ad libitum diet.
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.
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:The hypothesis tested in the present study was The effect fo weight loss by dietary intervention with very low calorie diet on colorectal inflammatory genes and genepathways. The study results have shown that a 10% weight loss in obese women down-regulated inflammatory and cancer gene pathways. In addition there was downregulation of transcription factors known to play an important role in colorectal cancer. Total RNA obtained from colorectal mucosal biopsy samples
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.
Project description:The aim of this study is to design and validate a test, METAHEALTH-TEST, based on gene expression analysis in blood cells, to quickly and easily analyse metabolic health. This test will be used to analyse metabolic improvement in overweight/obese individuals and in metabolically obese normal-weight (MONW) individuals after undergoing a weight loss intervention and/or an intervention for improvement in eating habits and lifestyle. Obesity and its medical complications are a serious health problem today. Using peripheral blood mononuclear cells (PBMC) as an easily obtainable source of transcriptomic biomarkers would allow to deepen into the knowledge of adaptations in response to increased adiposity that occur in internal homeostatic tissues, without the need of using invasive biopsies. Moreover, if PBMC were able to reflect lipid metabolism gene expression pattern recovery as a result of weight loss, it would provide valuable information to know the efficacy of therapies aimed at weight loss and, in any case, it would allow to personalize them according to the evolution of obese patients until the desired metabolic recovery is achieved.
Project description:The effect of a short-term calorie restricted diet was evaluated in six strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age Tissues were collected from mice at 22 weeks of age; there were 96 microarrays used in total: for each of the 6 strains of mice, there were 8 control-fed mice and 8 calorie restricted mice (one individual mouse per microarray)