Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity

ABSTRACT: Obesity is characterized by accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys). These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRβ repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest that dysglycemia in individuals with obesity is associated with recirculation of a heterogeneous population of partially dysfunctional PD-1+CD4 Tconv cells. These changes may contribute to the inter-organ crosstalk underlying IR

ORGANISM(S): Homo sapiens

PROVIDER: GSE237338 | GEO | 2024/02/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity

Project description:Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity

| PRJNA994606 | ENA

The epigenetic signature of systemic insulin resistance in obese women [OM]

Project description:Impaired ability of insulin to stimulate cellular glucose uptake and regulate metabolism, that is insulin resistance (IR), links adiposity to metabolic disorders such as type 2 diabetes (T2D), dyslipidemia and cardiovascular disease (Langenberg, 2012). Both genetic and epigenetic factors are implicated in development of systemic IR (Vaag, 2001). IR is characterized by elevated levels of fasting insulin in the general circulation. The aim of this study is to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by global CpG methylation and gene expression profiling in subcutaneous and visceral adipose tissue. A secondary aim is to determine whether the DNA methylation signature in peripheral blood mononuclear cells reflect WAT methylation, and can be used as marker for systemic IR. DNA methylation was analyzed in DNA extracted from SAT (subcutaneous adipose tissue) and VAT (visceral adipose tissue) pieces, as well as PBMCs (peripheral blood mononuclear cells), using the Infinium Human Methylation 450 BeadChip assay. This data is from VAT (omental).

2016-08-01 | E-GEOD-76394 | biostudies-arrayexpress

A dynamic subcutaneous adipose transcriptome of human insulin resistance identifies a molecular predisposition shared with visceral adipose tissue

Project description:Subcutaneous adipose tissue (SAT) is classically viewed as a metabolic buffer for lipid deposition during positive caloric balance, while visceral adipose tissue (VAT) is viewed as the dominant contributor and prime mediator of insulin resistance (IR) and cardiometabolic disease risk. Nevertheless, a growing body of data suggests that similar morphologic and molecular changes may occur in SAT as in VAT during obesity. In addition, while pro-inflammatory immune changes within adipose are thought to drive IR there is increasing data implicating a role for adipocytes and stromal populations especially in humans. Here, we identified a transcriptional landscape of IR in SAT of 220 humans across the spectrum of obesity and IR states, highlighting a broad range of metabolic pathways central to IR. Using single cell and nucleus deconvolution and statistical learning techniques, we identified a 35-gene signature that (1) achieved high predictive accuracy for homeostatic model of IR (HOMA-IR) across BMI; (2) was expressed across a variety of non-immune cell populations (most prominently adipocytes and adipocyte stem and precursor cells [ASPCs]), with primarily “protective” IR associations for adipocyte transcripts and “deleterious” associations for macrophage transcripts; (3) displayed a high concordance between SAT and VAT (greater than non-IR associated genes). Multiple SAT genes exhibited dynamic expression 5-years after weight loss surgery and with insulin stimulation. Finally, using available expression quantitative trait loci in SAT and/or VAT, we demonstrate similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI, suggesting underlying similarities in genetic determinants of IR between adipose depots. These results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and that is shared with VAT, nuancing the current VAT-centric concept of IR in humans.

2024-10-19 | GSE245948 | GEO

Transcriptional profiling of Regulatory T (Treg) cells and CD4+ conventional T (Tconv) cells from vTreg53 TCR transgenic and PPARg reporter mice

Project description:We reported transcriptional characterization of Treg and Tconv cells from thymic, splenic, and visceral adipose tissue (VAT) of vTreg53 TCR transgenic mice and control littermates. We examined the effect of Foxp3 on splenic and VAT CD4+ T cell transcriptome. We profiled gene expression in a novel PPARg+ splenic Treg population. We uncovered that the characteristic phenotype of VAT Treg cells was acquired in two stages.

2018-06-08 | GSE113393 | GEO

The epigenetic signature of systemic insulin resistance in obese women [BL]

2016-08-01 | E-GEOD-76285 | biostudies-arrayexpress

The epigenetic signature of systemic insulin resistance in obese women [SC]

2016-08-01 | E-GEOD-76398 | biostudies-arrayexpress

Metabolic control in VAT by Tregs through OSM-mediated suppression of adipogenesis

Project description:Regulatory T cells (Tregs) play diverse roles in tissue homeostasis. In visceral adipose tissue (VAT), resident Tregs, enriched with PPARγ, are clonally expanded in a IL-33 dependent manner. However, the tissue-specific functions of VAT Tregs, with unique transcriptome compared to spleen or other peripheral tissues, remain largely unknown. We identified two PPARγ+ mesenchymal stromal cells in VAT (VmSCs), named VmSC4s (PPARγ+Thy1-) and 5s (PPARγ+Thy1+). Lineage-tracing and transcriptome analysis revealled that VmSC4s contain precursors for VmSC5s. We also demonstrated that VAT Tregs directly suppress adipogenic differentation of VmSC5s through Oncostain M (OSM) to promote insulin sensitivity and glucose tolerance. Thus, VAT-Treg-derived OSM and VmSCs-displayed OSMR maintain tissue homeostasis via limiting the differentiation of dysfunctional adipocytes, which provide therapeutic targets for treating obesity and diabetes.

2023-08-01 | GSE226889 | GEO

Single-cell Analysis of Subcutaneous Fat Reveals Pro-fibrotic Cells that Correlate with Visceral Adiposity in HIV

Project description:Cardiometabolic diseases are common in persons with HIV (PWH) on antiretroviral therapy (ART), which has been attributed to preferential lipid storage in visceral adipose tissue (VAT) compared with subcutaneous adipose tissue (SAT). However, the relationship of SAT-specific cellular and molecular programs with VAT volume is poorly understood in PWH. We characterized SAT cell-type specific composition and transcriptional programs that are associated with greater VAT volume in PWH on contemporary ART. We enrolled PWH on long-term ART with a spectrum of metabolic health.We enrolled PWH on long-term ART with a spectrum of metabolic health. Ninety-two participants underwent SAT biopsy for bulk RNA sequencing and 43 had single-cell RNA sequencing. Computed tomography quantified VAT volume and insulin resistance was calculated using HOMA2-IR. VAT volume was associated with HOMA2-IR (p<0.001). Higher proportions of SAT intermediate macrophages (IMs), myofibroblasts, and MYOC+ fibroblasts were associated with greater VAT volume using partial Spearman’s correlation adjusting for age, sex, and body mass index (r =0.34-0.49, p<0.05 for all). Whole SAT transcriptomics showed PWH with greater VAT volume have increased expression of extracellular matrix (ECM)- and inflammation-associated genes, and reduced expression of lipolysis- and fatty acid metabolism-associated genes. In PWH, greater VAT volume is associated with higher proportion of SAT IMs and fibroblasts, and a SAT ECM and inflammatory transcriptome, which is similar to findings in HIV-negative persons with obesity. These data identify SAT cell-type specific changes associated with VAT volume in PWH that could underlie the high rates of cardiometabolic diseases in PWH, though additional longitudinal studies are needed to define directionality and mechanisms.

2024-05-22 | GSE243957 | GEO

miRNA expression data from lean PCOS adipose vs BMI matched control women

Project description:Why ~70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR), above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT), remains a fundamental question. In these experiments, we sought to explore the role of miRNAs in the AT of PCOS and matched controls. Analysis determined that PCOS AT has a differentially expressed miRNA profile, including upregulated miR-93. We observed a significant association between HOMA-IR, and GLUT4 and miR-93 expression in human AT. Our results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93, and demonstrate upregulated miR-93 expression in PCOS, possibly accounting for the IR of the syndrome, and also in non-PCOS women with IR. We performed miRNA microarrays to determine PCOS-related miRNA expression in adipose derived from lean PCOS patients and matched control women. We analyized miRNA from total RNA extracted from subcutaneous (sc) adipose tissue from three lean PCOS patients and three matched control women.

2012-09-06 | E-GEOD-37914 | biostudies-arrayexpress

Organ-specific metabolic pathways distinguish prediabetes, type 2 diabetes and normal tissues

Project description:Defects in pancreatic islets and the progression of multi-tissue insulin resistance in combination with environmental factors are the main causes of type 2 diabetes (T2D). Mass spectrometry-based proteomics of five key-metabolic tissues on a cohort of 42 multi-organ donors provided deep coverage of the proteomes of pancreatic islets, visceral adipose tissue (VAT), liver, skeletal muscle and serum. Enrichment analysis of gene ontology (GO) terms built a tissue-specific map of the chronological order of altered biological processes across healthy controls (CTRL), pre-diabetes (PD) and T2D subjects. This unique dataset allowed us to explore alterations of entire biological pathways and individual proteins in multiple tissues. We confirmed the significant decrease of the citric acid cycle and the respiratory electron transport in VAT and muscle of T2D and we provided a thorough visual representation of the complete set of downregulated proteins. Importantly, we found widespread novel alterations in relevant biological pathways including the increase in hemostasis in pancreatic islets of PD, the increase in the complement cascade in liver and pancreatic islets of PD and the elevation in cholesterol biosynthesis in liver of T2D. Overall, our findings suggest inflammatory, immune and vascular impairments in pancreatic islets as potentially causal factors of insufficient insulin production and increased glucagon levels in the early stages of T2D. In contrast alterations in lipid metabolism and mitochondrial function in the liver and VAT/muscle, respectively, became evident later in manifest T2D. This first multi-tissue proteomic map indicates the temporal order of tissue-specific metabolic dysregulation in T2D development.

2022-10-12 | PXD027597 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data