Adipose tissue network analyses reveal negative association between GDF15 and BMI during weight management intervention.
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ABSTRACT:
PROVIDER: PRJNA592713 | ENA |
REPOSITORIES: ENA
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Project description:CONTEXT: Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. OBJECTIVE: To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during three steps of a two-phase dietary intervention (DI). RESULTS: During LCD, 5 modules were found, 3 of which including at least 1 bio-clinical variable. Especially, the change in BMI was connected to changes in mRNA level of genes with Inflammatory response signature. In this module, BMI was negatively connected to several genes encoding secreted proteins including GDF15, CCL3 and SPP1. Whatever the phase of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. CONCLUSION: network analyses confirm GDF15 as upregulated with calorie restriction-induced weight loss, concomitantly to macrophages markers.
2020-04-01 | GSE141221 | GEO
Project description:Anorexia and other side effects of chemotherapy significantly limit the clinical applications of these chemotherapeutic agents, with underlying mechanisms still unclear. A growing body of research reveals that elevated levels of circulating GDF15 after chemotherapy are essential in initiating anorexia and other side effects by activating GFRAL+ neurons in the brainstem. However, the full array of context-dependent transcriptional regulators controlling Gdf15 expression remains to be defined. This study reports that chemotherapy drugs acutely stimulate liver GDF15 production via selective activation of the hepatic stress sensor IRE1α, thereby controlling circulating GDF15 levels. Genetic ablation of hepatic IRE1α reduces circulating GDF15 and alleviates anorexia and body weight loss following chemotherapy drug treatments in tumor-bearing mice. Mechanistically, chemotherapy drugs activate hepatic IRE1α RNase activity to produce the active form of the transcription factor XBP1 to promotes the expression of Gdf15 gene in hepatocytes. Moreover, treatment with pharmacological IRE1α RNase inhibitor effectively suppresses liver Gdf15 expression and circulating GDF15 levels, resulting in improvements in chemotherapy-induced anorexia and body weight loss. Our results reveal a stress-responsive mechanism that mediates communication between the liver and brain. This mechanism can be targeted pharmacologically to alleviate anorexic side effects that accompany chemotherapy-induced body weight loss.
2024-04-22 | GSE235695 | GEO
Project description:We conducted a genome-wide placental transcriptome study aiming at the identification of functional pathways representing the molecular link between maternal pre-pregnancy BMI and fetal growth. We used RNA microarray (Agilent 8 X 60 K), medical records, and questionnaire data from 183 mother-newborn pairs from the ENVIRONAGE birth cohort study (Flanders, Belgium). We applied a weighted gene co-expression network analysis (WGCNA) and identified genes modules and hub genes that were associated with maternal BMI as well as newborn birth weight. Modules of interest were further characterized by gene ontology (GO) and pathway enrichment analyses. We assessed the mediating effects of modules and hub genes in the association between maternal BMI and newborn weight.
2019-03-16 | GSE128381 | GEO
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.
2017-07-21 | GSE95624 | GEO
Project description:This trial studies how well weight management and health behavior intervention works in helping patients with hereditary breast and ovarian cancer and Lynch syndrome mutation carriers lose or maintain a healthy weight and lower their risk for cancer. Lifestyle behaviors such as physical activity, diet, and weight management may play a key role in preventing cancers and improving outcomes even in those with hereditary cancer syndromes.
| 2319071 | ecrin-mdr-crc
Project description:Growth Differentiation Factor 15 (GDF15) is a divergent member of the TGF-β superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine BPD models, and GDF15 loss exacerbates oxidative stress and decreases viability in vitro in pulmonary epithelial and endothelial cells. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal Gdf15-/- mice and wild-type (WT) controls on a similar background to room air or hyperoxia (95% O2) for 5 days after birth. The mice were euthanized on PND 21. Gdf15 -/- mice had higher mortality and lower body weight than WT mice after exposure to hyperoxia. Upon exposure to hyperoxia, female mice had higher alveolar simplification in the Gdf15-/- group than the female WT group. Gdf15-/- and WT mice showed no difference in the degree of the arrest in angiogenesis upon exposure to hyperoxia. Gdf15-/- mice showed lower macrophage count in the lungs compared to WT mice. Our results suggest that Gdf15 deficiency decreases the tolerance to hyperoxic lung injury with evidence of sex-specific differences.
2023-07-20 | GSE211744 | GEO
Project description:Cancer cachexia is a disorder characterized by both involuntary weight loss and impaired physical performance. Decline in physical performance of patients with cachexia is associated with poor quality of life, and currently there are no effective pharmacological interventions that restore physical performance. Here we examined the effect of GDF15 neutralization in a mouse model of cancer-induced cachexia (TOV21G) that manifested weight loss and muscle function impairments. With comprehensive assessments, our results demonstrated that cachectic mice treated with the anti-GDF15 antibody mAB2 exhibited body weight gain with near-complete restoration of muscle mass and markedly improved muscle function and physical performance. Mechanistically, the improvements induced by GDF15 neutralization were primarily attributed to increased caloric intake, while altered gene expressions in cachectic muscles were restored in both caloric intake-dependent and -independent manners. The findings implicate the potential of GDF15 neutralization as an effective therapy to enhance physical performance of patients with cachexia.
2023-01-11 | GSE214603 | GEO
Project description:The aim of study was to investigate correlation bewteen peripheral blood mononuclear cell (PBMC) transcriptome profiles and plasma lipid profiles of Korean adult with varying BMI. In Korean, BMI cut-off points are 18.5~22.9 kg/m2 (normal range), M-bM-^IM-% 23 kg/m2 (overweight), M-bM-^IM-% 25 kg/m2 (obese), M-bM-^IM-% 30 kg/m2 (severely obese). Thus, the obese group was subdivided into mildly obese (BMI 25~27 kg/m2, OA) and highly obese (BMI 27~30 kg/m2, OB). This study indicates that lipid, glucose and inflammation metabolism-related gene expressions were altered according to cahnge of varing phenotype biomarkers such as BMI, plasma total-C, TG, FFA and HDL-C. Thus, blood biomarkers and PBMC gene expression profiles identified in this study may be useful as indicative biomarkers for obese susceptibility in Korean adult as well as response to various intervention for treating obesity. Total RNA of PBMCs was obtained from normal weight, obese person and mRNA expression was measured.
2014-06-01 | E-GEOD-55205 | biostudies-arrayexpress
Project description:Purpose: To identify, using RNA-sequencing, differentially expressed genes in the white adipose tissue in obesity and in response to lipid intervention in both normal weight and obese individuals. Methods: White adipose tissue mRNA profiles of normal weight and obses humans at baseline (0-weeks) and 12-weeks after fish oil (3d/day of which 1.1g EPA and 0.8g DHA) or corn oil (3g/day) supplementation were generated by deep sequencing using RNA sequencing. The sequence reads that passed quality filters were aligned to the human genome using TopHat and analyzed at the gene level using DESeq2. qRT–PCR validation was performed using Taqman probe assays Results: Using an optimized data analysis workflow, we mapped reads to the human genome (hg38.0) and identified 789 genes differentially expressed between normal weight and obese individuals at baseline (week-0) (adjusted p value <0.05 and fold change >2). 623 of these were upregulated and 175 were downregulated. Geneset enrichment analysis identified several enriched pathways, including regulation of immune and inflammatory response, tissue growth and glucose metabolism in obese indvidiuals in comparison to normal weight. We identified 26 genes differentially expressed in normal weight individuals in response to fish oil intervention (week-12) (adjusted p value <0.05 and fold change >1). 14 of these were upregulated and 12 were downregulated. We identified 8 genes differentially expressed in obese individuals in response to fish oil intervention (week-12) (adjusted p value <0.05 and fold change >1). 3 of these were upregulated and 5 were downregulated. Geneset enrichment analysis identified several enriched pathways, including regulation of immune and inflammatory response in both normal weight and obese individuals in response to fish oil intervention with greater effects in normal weight individuals. Conclusions: Our study provides novel insights into the association of obesity and changes to the human white adipose tissue transcriptome, in addition to the effects of fish oil (EPA and DHA) on the transcriptome of normal weight and obese individuals and differences in response between these BMI subgroups. Our study further identifies putative gene targets and molecular pathways that help to understand how obesity results in adipose tissue dysfunction and how EPA and DHA may modulate the long term expression of gene networks and disease pathways related to onset of obesity associated inflammation.
2021-02-24 | GSE162653 | GEO
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
2017-04-04 | PXD005216 | Pride