Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adipocyte Epigenetic Alterations and Potential Therapeutic Targets in Transgenerationally Inherited Lean and Obese Phenotypes Following Ancestral Exposure to Environmental Toxicants

ABSTRACT: This study examines the transgenerational adipocyte (fat cell) epigenetic alterations in F3 generation obese and lean rats ancestrally exposed to DDT and atrazine. Adipocytes were isolated from the gonadal fat pad of F3 generation 1-year old rats ancestrally exposed to DDT, atrazine, or vehicle control in order to obtain adipocyte DNA for DNA methylation analysis. Observations indicate that there were differential DNA methylated regions (DMRs) in the adipocytes with the lean or obese phenotypes compared to control normal (non-obese or lean) populations. Interestingly, there were epigenetic changes that were distinct when comparing the lean and obese DMRs between the control and exposure lineage groups. DMR gene associations were identified which included common set of genes previously shown to associate with adipocyte pathology. The comparison of epigenetic alterations indicated that there were substantial overlaps between the different treatment lineage groups for both the lean and obese phenotypes. Novel correlated genes and gene pathways associated with DNA methylation were identified, and may aid in the discovery of potential therapeutic targets for metabolic diseases such as obesity.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE137536 | GEO | 2019/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination and the incidence of adult onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the F3 generation males were investigated. No pathology was observed in the F1 generation DDT lineage males or females compared with F1 generation controls (vehicle exposure). There was an increase of testis disease and early onset puberty in the F2 generation DDT lineage males. The F3 generation DDT males had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had significant increases in ovarian and kidney disease. Both the F3 generation males and females had significant increases in the frequency of obesity and multiple disease. The F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, kidney disease, and multiple disease pathologies.

2018-07-31 | GSE114032 | GEO

Atrazine Induced Epigenetic Transgenerational Inheritance of Disease, Lean Phenotype and Sperm Epimutation Pathology Biomarkers

Project description:This study examined the potential transgenerational actions of the herbicide atrazine. The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease, increased frequency of tumor development in males and females (predominately mammary tumors), early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations and a lean phenotype in males and females involving a reduced adipocyte size, decreased body mass index (BMI) and reduced adiposity. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified. A comparison of control versus atrazine lineage sperm identified 519 DMRs (p<10-6) for the F1 generation, 431 DMR (p<10-5) for the F2 generation, and 958 DMR (p<10-9) for the transgenerational F3 generation sperm.

2017-08-08 | GSE98683 | GEO

f99e97b0-359a-40b8-aaef-30c63cc77d85 - samples

Project description:94 human adipocyte samples isolated from whole adipose tissues using collagenase digestion of tissue and flotation of lipid-laden adipocytes, followed by RNA isolation and RNA sequencing (SMARTer Stranded Total RNA-Seq library preparation, HiSeq 4000 100-bp paired-end reads). Adipocyte samples comprise subcutaneous and visceral adipocytes isolated from obese and lean people (N=24 obese-subcutaneous, N=24 obese-visceral, N=22 control-subcutaneous, N=24 control-visceral). Human adipocyte RNA sequencing data are provided as BAM files.

| EGAD00001010195 | EGA

Transcription profiling of human abdominal subcutaneous adipocytes from obese and non-obese Pima Indians

Project description:Microarray analysis comparing gene expression profiles of adipocytes from non-diabetic lean vs non-diabetic obese Pima Indian subjects to identify differentially expressed adipocyte genes with obesity. RNA samples of isolated abdominal subcutaneous adipocytes from 20 lean (10 Males / 10 Females, aged 31Â±6 year, Body Mass Index 25Â±3 kg/m2 ) and 19 obese (9M/10F, 29Â±5y, 55Â±8 kg/m2 ) subjects were hybridized individually to Affymetrix oligonucleotide arrays HG-U95A, B, C, D, and E.

2007-08-25 | E-GEOD-2508 | biostudies-arrayexpress

Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral DDT Exposure

Project description:In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.

2019-01-19 | GSE121585 | GEO

Transcriptome profile of subcutaneous adipocytes isolated from obese vs. lean postmenopausal women

Project description:Adipocytes isolated from lean and obese postmenopausal women with no significant differences in metabolic syndrome parameters demonstrate changes in multiple inflammatory, metabolic and structural gene families. Purified adipocyte samples were isolated from subcutaneous adipose tissue surgical biopsies of 7 obese (BMI>30) and 7 lean (BMI<25) postmenoposal women and gene expression was quantified with Agilent-014850, 4X44K human whole genome platform arrays (GPL6480)

2013-02-02 | E-GEOD-44000 | biostudies-arrayexpress

Expression profiling in adipocytes of obese humans

Project description:Microarray analysis comparing gene expression profiles of adipocytes from non-diabetic lean vs non-diabetic obese Pima Indian subjects to identify differentially expressed adipocyte genes with obesity. RNA samples of isolated abdominal subcutaneous adipocytes from 20 lean (10 Males / 10 Females, aged 31±6 year, Body Mass Index 25±3 kg/m2 ) and 19 obese (9M/10F, 29±5y, 55±8 kg/m2 ) subjects were hybridized individually to Affymetrix oligonucleotide arrays HG-U95A, B, C, D, and E. Keywords = adipocyte Keywords = obesity Keywords = inflammation Keywords = gene expression Keywords: other

2006-01-01 | GSE2508 | GEO

Environmental Toxicant Induced Epigenetic Transgenerational Inheritance of Ovarian Pathology and Granulosa Cell Epigenome and Transcriptome Alterations: Ancestral Origins of PCO and POI

Project description:Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease, including decreases in the primordial follicle pool of oocytes that are similar to what is seen in POI, and increases in ovarian cysts that are similar to what is seen in PCOS. In the current study, transgenerational changes to the epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures compared to controls. In purified granulosa cells from 20 day old F3 generation females 164 differentially methylated regions (DMRs) (p<1e-06) were found in the F3 generation vinclozolin lineage, and 293 DMRs (p<1e-06) in the DDT lineage, compared to controls.

2018-11-08 | GSE118381 | GEO

Genome-wide maps of Dnmt1-dependent DNA methylome in adipocytes

Project description:White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes. Particularly, genetic ablation of adipocyte Dnmt1, the major methylation writer, led to increased adiposity characterized by increased adipocyte hypertrophy along with reduced expansion of adipocyte precursors (APs). These effects of Dnmt1 deficiency provoked systemic hyperlipidemia and impaired energy metabolism both in lean and obese mice. Mechanistically, Dnmt1 deficiency abrogated mitochondrial bioenergetics by inhibiting mitochondrial fission and promoted aberrant lipid metabolism in adipocytes, rendering adipocyte hypertrophy and WAT dysfunction. Dnmt1-dependent DNA methylation prevented aberrant CTCF binding and, in turn, sustained the proper chromosome architecture to permit interactions between enhancer and dynamin-related protein gene Drp1 in adipocytes. Also, adipose DNMT1 expression inversely correlated with adiposity and markers of metabolic health, but positively correlated with AP-specific markers in obese human subjects. Thus, these findings support strategies utilizing Dnmt1 action on mitochondrial bioenergetics in adipocytes to combat obesity and related metabolic pathology.

2021-03-24 | GSE158944 | GEO

Ancestral Plastics Exposure Induces Transgenerational Disease Specific Sperm Epigenome-Wide Association Biomarkers Methylation Epimutation Biomarkers for Specific Transgenerational Disease

Project description:Plastic derived compounds are one of the most frequent daily world-wide exposures. Previously a mixture of plastic derived toxicants involving bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP) at lower dose exposures of a gestating female rat were found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation) and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations show disease specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease specific DMR associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.

2021-03-16 | GSE163412 | GEO

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