Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE25402 | GEO | 2012/08/13
SECONDARY ACCESSION(S): PRJNA134139
REPOSITORIES: GEO
Similar Datasets
Project description:In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate adipose inflammation by attracting the migration of inflammatory cells into the tissue. Using an unbiased approach, we identified adipose microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role in controlling CCL2 production. In subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present in all subjects and downregulated in obesity. Of these, 10 affected adipocyte CCL2 secretion in vitro and for 2 miRNAs (miR-126 and miR-193b), regulatory circuits were defined. While miR-126 bound directly to the 3'-untranslated region of CCL2 mRNA, miR-193b regulated CCL2 production indirectly through a network of transcription factors, many of which have been identified in other inflammatory conditions. In addition, overexpression of miR-193b and miR-126 in a human monocyte/macrophage cell line attenuated CCL2 production. The levels of the two miRNAs in subcutaneous WAT were significantly associated with CCL2 secretion (miR-193b) and expression of integrin, α-X, an inflammatory macrophage marker (miR-193b and miR-126). Taken together, our data suggest that miRNAs may be important regulators of adipose inflammation through their effects on CCL2 release from human adipocytes and macrophages.
| S-EPMC3402332 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE25401: Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity [gene expression] GSE25470: Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity [miRNA data] GSE25910: Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity [differentiation data] Refer to individual Series
2012-08-12 | E-GEOD-25402 | biostudies-arrayexpress
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity. Abdominal subcutaneous adipose needle biopsies were obtained from women (n=56) with a wide variation in BMI. From the biopsies we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.0 ST Arrays (Affymetrix Inc., Santa Clara, CA), labelled RNA to Affymetrix miRNA arrays, and bisulphite converted DNA to Illumina Infinium HumanMethylation27 beadchips using standardised protocols (Affymetrix Inc., Illumina Inc.) . Subsequent analyses of gene expression was performed using the Affymetrix GeneChip Operating Software version 1.4. To allow comparisons of transcript levels between samples, all samples were subjected to an all-probeset scaling-to-target signal of 100.
2012-08-12 | E-GEOD-25401 | biostudies-arrayexpress
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity. Abdominal subcutaneous adipose needle biopsies were obtained from women (n=56) with a wide variation in BMI. From the biopsies, total RNA was isolated and labelled using the FlashTag biotin HSR labeling kit (Genisphere Inc., Hatfield, PA) according to the supplier's protocol. The labelled samples were placed in a hybridization cocktail mix containing 4% formamide and hybridised overnight to Affymetrix miRNA Arrays (Affymetrix Inc.) following the indicated Genisphere protocol. The arrays were washed, stained and scanned in an Affymetrix GCS 3000 scanner. Signal intensities and present calls were generated by using the microRNA QC tool by Affymetrix.
2012-08-12 | E-GEOD-25470 | biostudies-arrayexpress
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity. Subcutaneous adipose tissue was obtained from healthy subjects undergoing cosmetic liposuction (n=12). There was no selection for age, sex or BMI. From the tissue, we isolated preadipocytes and in vitro differentiated them to adipocytes. The cells were lysed at day 4/5 (early), 8 (middle) and 12 (late) of differentiation. From the samples, we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.0 ST Arrays (Affymetrix Inc., Santa Clara, CA). Pre-processing was performed using the Affymetrix Expression Console version 1.1 and the following settings: Summarization: PLIER; Background Correction: PM-GCBG; Normalization: Global Median.
2012-08-12 | E-GEOD-25910 | biostudies-arrayexpress
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
2012-08-13 | GSE25470 | GEO
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
2012-08-13 | GSE25910 | GEO
Project description:We used an unbiased systems biology approach to study the regulation of gene expression in human adipose tissue focusing on inflammation. We show that microRNAs play a major role as regulators of CCL2 production in obesity.
2012-08-13 | GSE25401 | GEO
Project description:Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity
| PRJNA134139 | ENA
Project description:BackgroundN6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution.MethodsWe extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT) N=48; subcutaneous adipose tissue (SAT) N=56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (N=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in METTL3 and YTHDF3 from genome wide data from the Sorbs population (N=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits.ResultsIn adipose tissue we observed that several m6A regulators (WTAP, VIRMA, YTHDC1 and ALKBH5) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for METTL3, WTAP, VIRMA, FTO and YTHDC1. In PBMCs, we identified ALKBH5 and YTHDF3 correlated with obesity. Genetic markers in METTL3 associate with BMI whilst SNPs in YTHDF3 are associated with its gene expression.ConclusionsOur data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.
| S-EPMC8689137 | biostudies-literature