Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [ChIP-Seq]

ABSTRACT: Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling proein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a cis-regulatory variant rs47238345 that is responsible for differential Ucp1 expression. The alternative T allele of rs47238345 at the Ucp1 -12kb enhancer in 129 facilitates the allele-specific binding of nuclear factor I-A (NFIA) to mediate allele-specific enhancer-promoter interaction and Ucp1 transcription. We also identified Lim homeobox protein 8 (Lhx8), whose expression is higher in 129 than in B6, as a trans-acting regulator of Ucp1 in mice and humans. These results demonstrate the cis- and trans-acting effects of genetic variation on Ucp1 expression that underlie phenotypic diversity.

ORGANISM(S): Mus musculus

PROVIDER: GSE186904 | GEO | 2022/07/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [WGS]

Project description:Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling proein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a cis-regulatory variant rs47238345 that is responsible for differential Ucp1 expression. The alternative T allele of rs47238345 at the Ucp1 -12kb enhancer in 129 facilitates the allele-specific binding of nuclear factor I-A (NFIA) to mediate allele-specific enhancer-promoter interaction and Ucp1 transcription. We also identified Lim homeobox protein 8 (Lhx8), whose expression is higher in 129 than in B6, as a trans-acting regulator of Ucp1 in mice and humans. These results demonstrate the cis- and trans-acting effects of genetic variation on Ucp1 expression that underlie phenotypic diversity.

2022-07-27 | GSE188261 | GEO

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [HiC]

2022-07-27 | GSE188260 | GEO

NFIA determines the cis-effect of genetic variation on adipocyte browning in mice [RNA-Seq]

2022-07-27 | GSE186903 | GEO

RNA-Sequencing of wild type and UCP1-null beige adipose tissue

Project description:Since brown adipose tissue (BAT) dissipates energy through UCP1, BAT has garnered attention as a therapeutic intervention for obesity and metabolic diseases including type 2 diabetes. As we better understand the roles of classical brown and beige adipocytes, increased beige fat mass in response to a variety of external/internal cues is associated with significant improvements in glucose and lipid homeostasis that may not be entirely mediated by UCP1. We aim to analyze transcriptome of wild type and UCP1-null beige adipocyte to identify the UCP1-independent function.

2017-10-28 | E-MTAB-4085 | biostudies-arrayexpress

Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice [ChIP-Seq]

Project description:Obesity causes insulin resistance, and PPARγ ligands like rosiglitazone (rosi) are insulin-sensitizing, yet mechanisms remain unclear. High fat diet (HFD) induced obesity has major effects on visceral epididymal adipose tissue (eWAT) of C57BL/6 (B6) mice, and here we report altered activity of gene regulatory elements with changes in PPARγ genome-wide occupancy. Treatment with rosi restored insulin sensitivity, yet surprisingly had little effect on eWAT, leading us to consider the subcutaneous inguinal fat (iWAT). In this depot, rosi markedly induced molecular signatures of brown fat including the key thermogenic gene Ucp1. Obesity-resistant 129S1/SvImJ (129) mice showed this degree of iWAT browning even in the absence of rosi. Remarkably, the 129 Ucp1 locus had increased PPARγ binding and gene expression that was preserved in B6x129 F1 intercross iWAT, with imbalance favoring the 129-derived alleles showing a cis-acting genetic difference. Thus, B6 mice have a genetic defect in Ucp1 expression. However, imbalanced expression favoring 129 over B6 was nearly lost when Ucp1 was activated by rosi, or by iWAT browning in cold-exposed or young mice. These results provide a novel framework for understanding how environmental influences like drugs can rescue genetically determined disease phenotypes by affecting the epigenome.

2017-02-27 | GSE92606 | GEO

Epigenomic rescue of genetically defective Ucp1 expression in subcutaneous fat of C57BL/6 mice [RNA-Seq]

2017-02-27 | GSE91067 | GEO

UCP1-dependent depletion of liver extracellular succinate antagonizes inflammatory pathogenesis

Project description:Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide and is intimately linked with obesity and type 2 diabetes. Liver inflammation is a hallmark of NAFLD and is thought to contribute to tissue fibrosis and disease pathogenesis. Uncoupling protein 1 (UCP1) is exclusively expressed in brown and beige adipocytes and has been extensively studied for its capacity to elevate thermogenesis and reverse obesity. Here we identify an endocrine pathway regulated by UCP1 that antagonizes liver inflammation and pathology, independent of effects on obesity. We show that, without UCP1, brown and beige fat exhibit a diminished capacity to clear succinate from the circulation. Moreover, UCP1KO mice exhibit elevated extracellular succinate in liver tissue that drives inflammation through ligation of its cognate receptor succinate receptor 1 (SUCNR1) in liver-resident stellate cell and macrophage populations. Conversely, increasing brown and beige adipocyte content in mice antagonizes SUCNR1-dependent inflammatory signaling in the liver. We show that this UCP1-succinate-SUCNR1 axis is necessary to regulate liver immune cell infiltration and pathology, and systemic glucose intolerance in an obesogenic environment. As such, the therapeutic utility of brown and beige adipocytes, and UCP1, extends beyond thermogenesis and may be leveraged to antagonize NAFLD and SUCNR1-dependent liver inflammation.

2022-02-17 | PXD024717 | Pride

Immortalized clonal brown, beige and white adipose cell lines

Project description:Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of “beige” cells from murine white fat depots. Microarray analysis of the differentiated clonal inguinal and interscapular adipocytes in the presence of forskolin (10mM). These samples were profiled using Affymetrix mouse 430 2.0 arrays, 26 samples in total.

2012-07-23 | E-GEOD-39562 | biostudies-arrayexpress

scATAC-seq of Inguinal Adipose Tissue of UCP1-KO and WT mice.

Project description:Single cell level analysis of transcriptional circuits regulating UCP1-indepednent theremogensis through Lgr6 in inguinal Adipose tissue. We previously identified an increase in Lgr6 gene expression in the beige adipocyte population of UCP1-KO mice and hypothesized its involvement in UCP1-independent thermogensis. Consistent with our previous data the scATAC-seq data reveals that chromatin accessibility at the Lgr6 loci is significantly higher in Ucp1- KO beige adipocytes as compared to WT and the promter is also more accessible in Ucp1- KO beige adipocytes. Other DNA-binding motifs involved in UCP-1 indepedent thermogensis were also analyzed and found to be upregulated in the KO model.

2021-05-15 | GSE174456 | GEO

Browning of White Adipose Tissue with Roscovitine Induces a Distinct Population of UCP1+ Adipocytes.

Project description:Analysis of FACS sorted UCP1+ adipocytes shows that the mRNA signature of brite adipocytes is distinct from beige adipocytes, which arise through catecholamine signaling.

2016-12-13 | GSE87191 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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