Okinawa Diabetic microbiome
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ABSTRACT:
PROVIDER: PRJEB63608 | ENA |
REPOSITORIES: ENA
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Project description:Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia leads to non-proliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retinal barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas express PLIN2, a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from T2DM patients or with palmitate concentrations typical of T2DM plasma, but not under high glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induce capillary degeneration in ex vivo explants, which was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study provides a novel mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target to inhibit lipid-activated MPs in DR
2023-08-31 | GSE239512 | GEO
Project description:In a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on abdominal subcutaneous adipose tisse gene expression. We studied obese adults with features of the metabolic syndrom, n=56. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks. Gene expression was analyzed using linear mixed-effects models including specific genes as dependent variable, subject identifier as a random effect, and body weight, age, gender, study centre (i.e. also study duration), study group, time-point and study group * time-point interaction as covariates. 128 genes were significantly different regulated by the two diets with a FDR of 24%. TThese genes were overrepresented in pathways related to immune response. I conclusion, a Healthy Nordic diet reduces inflammatory gene expression in abdominal subcutaneous adipose tissue. This could contribute to beneficial influences on lipid metabolism and cardiovascular disease.
2015-01-26 | GSE56716 | GEO
Project description:Cachexia is a wasting disorder of adipose tissues that leads to profound weight loss and frailty. One key characteristic of cachexia is elevated resting energy expenditure, which has been linked to increased fat lipolysis and thermogenesis.
2024-07-23 | GSE239524 | GEO
Project description:Quantitative measurement of circulating metabolites may help to identify tissue specific metabolic pathways that are modulated by or causal for a disease condition. The aim of the study was to explore associations between plasma lipid concentrations and gene expression in pancreatic β-cells and insulin target tissues in a mouse model of pre-diabetes to uncover molecular mechanisms and biomarkers of diabetes susceptibility.
2021-11-24 | GSE140369 | GEO
Project description:Quantitative measurement of circulating metabolites may help to identify tissue specific metabolic pathways that are modulated by or causal for a disease condition. The aim of the study was to explore associations between plasma lipid concentrations and gene expression in pancreatic β-cells and insulin target tissues in a mouse model of pre-diabetes to uncover molecular mechanisms and biomarkers of diabetes susceptibility.
2021-11-24 | GSE164672 | GEO
Project description:Primary outcome(s): Plasma concentrations of metabolites that have amino moieties and other metabolites
| 2645093 | ecrin-mdr-crc
Project description:Interventions: Gold Standard:Colonoscopy findings;Index test:wide-target metabolites and lipid biomarkers
Primary outcome(s): Sensitivity;Area under ROC curve
Study Design: Factorial
| 2701069 | ecrin-mdr-crc
Project description:Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes. Methods and Results---No significant correlation was found between leukocyte counts and plasma lipid levels in 74 individuals. Profiling and analyzing the leukocyte gene expression of 32 individuals revealed distinctive patterns in response to plasma lipid levels: 1) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol levels, and negatively correlated with high-density lipoprotein cholesterol levels; 2) genes involved in platelet activation were negatively correlated with high-density lipoprotein cholesterol levels; 3) transcription factors regulating lipidgenesis-related genes were correlated with plasma lipid levels; 4) a number of genes correlated to plasma lipid levels were found located in the regions of known QTLs associated with hyperlipemia. Conclusions--- We discovered interesting patterns of leukocyte gene expression in response to plasma lipid levels. Most importantly, genes involved in lipid metabolism, the electron transportation chain, and platelet activation were found correlated with plasma lipid levels. We suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in lipid and fatty acid metabolism, through the activation of key transcription factors, such as sterol regulatory element binding transcription factors and peroxisome proliferative activated receptors. Experiment Overall Design: 1. Profile gene expression in human peripheral blood cells. Experiment Overall Design: 2. Test blood biochemistry and blood cell differential counts Experiment Overall Design: 3. Examine the correlation between blood gene expression and blood lipid levels. Experiment Overall Design: 4. Explore possible pathways with significant genes. Experiment Overall Design: 5. Validate a number of significant genes with RT-PCR
2008-06-12 | E-GEOD-3059 | biostudies-arrayexpress
Project description:The Nordic Centre of Excellence Programme in Molecular Medicine (NCoEDG) is a joint venture between the Joint Committee of the Nordic Medical Research Councils (NOS-M), the Nordic Council of Ministers and the Nordic Research Board (NordForsk).
| EGAO00000000006 | EGA
Project description:In a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on abdominal subcutaneous adipose tisse gene expression. We studied obese adults with features of the metabolic syndrom, n=56. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks. Gene expression was analyzed using linear mixed-effects models including specific genes as dependent variable, subject identifier as a random effect, and body weight, age, gender, study centre (i.e. also study duration), study group, time-point and study group * time-point interaction as covariates. 128 genes were significantly different regulated by the two diets with a FDR of 24%. TThese genes were overrepresented in pathways related to immune response. I conclusion, a Healthy Nordic diet reduces inflammatory gene expression in abdominal subcutaneous adipose tissue. This could contribute to beneficial influences on lipid metabolism and cardiovascular disease. Abdominal subcutaneous adipose needle biopsies were obtained before (W0) and after completion (W18-24) of the dietary intervention. From the biopsies we extracted RNA. From total RNA we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.1 ST Arrays (Affymetrix Inc., Santa Clara, CA), and then washed, stained and scanned the slides using standardised protocols (Affymetrix Inc.).
2015-01-26 | E-GEOD-56716 | biostudies-arrayexpress