Mouse white adipose tissue HaloREVERBα ChIP-seq
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Mus musculus
SUBMITTER: Louise Hunter
PROVIDER: E-MTAB-10573 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. We perform in vivo antibody-independent ChIP-sequencing of endogenously-expressed REVERBα, in order to map its cistrome and so define its repressive targets. We find that REVERBα binding sites harbour consensus RORE or RevDR2 motifs, and overlap with corepressor complex binding, without over-representation of putative tethering factors. When Reverbα is deleted in a hepatocyte-selective fashion, only modest physiological and transcriptional effects are seen, with de-repressed target genes tightly associating with REVERBα binding sites. Thus, contrary to previous reports, REVERBα does not repress lipogenesis under basal conditions. REVERBα control of a more extensive transcriptional programme is revealed only by perturbation (the metabolically abnormal global Reverbα-/- mouse, or acutely mistimed feeding), supporting instead a role for this core clock protein in buffering against metabolic challenge.
2020-09-30 | E-MTAB-8413 | biostudies-arrayexpress
Project description:The circadian clock coordinates energy metabolism, with REVERBα considered a dominant regulator of lipid metabolism. REVERBα is a core clock protein, which demonstrates robust rhythmic expression across metabolic tissues. Here, we explore its role in white adipose metabolism, and propose that REVERBα plays a key part in the response of adipose to obesity. Mice globally lacking Reverbα (Reverbα-/-) display adiposity, increased susceptibility to diet-induced obesity, and up-regulation of the lipogenic proteome in white adipose depots. When Reverbα is deleted selectively in adipose (ReverbαFlox2-6AdipoCre), however, we observe only modest phenotypic and transcriptomic changes in the basal state, with altered regulation of clock and extracellular matrix (ECM) pathways. Thus the adipose-autonomous actions of REVERBα are shaped by context. On high-fat diet challenge, ReverbαFlox2-6AdipoCre mice accumulate more adipose mass than littermate controls, and are spared obesity-related inflammation. Gene expression analysis reveals pathways of lipid handling to be up-regulated. These findings therefore highlight a critical role for REVERBα in the regulation of adipose tissue expansion. Further, when transcriptomic data is integrated with the REVERBα cistrome, we detect strong associations of REVERBα binding sites, not only with the clock and ECM targets de-repressed under normal conditions, but with the broad range of metabolic genes unmasked as REVERBα targets by obesity. Thus our data favour a new interpretation of REVERBα function, not as conferring rhythmicity to lipogenesis, but as buffering against lipogenic cues asynchronous to the normal temporal routine.
2021-07-31 | E-MTAB-8840 | biostudies-arrayexpress
Project description:The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. We perform in vivo antibody-independent ChIP-sequencing of endogenously-expressed REVERBα, in order to map its cistrome and so define its repressive targets. We find that REVERBα binding sites harbour consensus RORE or RevDR2 motifs, and overlap with corepressor complex binding, without over-representation of putative tethering factors. When Reverbα is deleted in a hepatocyte-selective fashion, only modest physiological and transcriptional effects are seen, with de-repressed target genes tightly associating with REVERBα binding sites. Thus, contrary to previous reports, REVERBα does not repress lipogenesis under basal conditions. REVERBα control of a more extensive transcriptional programme is revealed only by perturbation (the metabolically abnormal global Reverbα-/- mouse, or acutely mistimed feeding), supporting instead a role for this core clock protein in buffering against metabolic challenge.
2020-09-30 | E-MTAB-8402 | biostudies-arrayexpress
Project description:Transcriptome analysis of epididymal white adipose tissue (WAT) depots in Ercc1 animals: To further elucidate the role of ERCC1 in WAT we scanned the transcriptome of 15 day old wt and Ercc1 epididymal WAT.
2013-11-04 | E-MEXP-3930 | biostudies-arrayexpress
Project description:An understanding of the mechanisms regulating white adipose tissue (WAT) formation is key for developing of new tools to treat obesity and its related diseases. Here, we identify DEPTOR as a positive regulator of adipogenesis whose expression is associated with obesity. In a polygenic mouse model of obesity/leanness, Deptor is part of the Fob3a QTL linked to obesity and we fine that Deptor is the highest priority candidate gene regulating WAT accumulation in this model. Using a doxycycline-inducible mouse model for Deptor overexpression, we confirmed that Deptor promotes WAT expansion in vivo. DEPTOR expression is elevated in WAT of obese humans and strongly correlates with the degree of obesity. We show that DEPTOR is induced during adipogenesis and that its overexpression cell-autonomously promotes, while its suppression blocks, adipogenesis. DEPTOR positively regulates adipogenesis by promoting the activity of the pro-adipogenic factors Akt/PKB and PPAR-gamma. These results establish DEPTOR as a physiological regulator of adipogenesis and provide new insights into the molecular mechanisms controlling WAT formation. 2 groups of F2 mice for opossing genotype at Fob3a QTL (FF versus VV) - parental strains of the F2 cross were the Fat line and congenic V-line; 5 biological replications per group; reference for Fat line: Horvat S. et al. (2000) MAMMALIAN GENOME 11(1): 2-7
2012-08-14 | E-GEOD-38321 | biostudies-arrayexpress
Project description:White adipose tissue (WAT) plays a critical role in whole-body energy homeostasis. In this study, we established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and in response to 8 weeks of high intensity interval training (HIIT). We combined a high-throughput and reproducible mass spectrometry-based proteomics pipeline and identified a total of 3773 proteins. We find that a majority of regulated proteins displayed progression from lean to obese and T2D individuals and were highly associated with clinical measures of glucose homeostasis (e.g., insulin sensitivity, HbA1c) and they could, therefore, serve as potential disease biomarkers. Interestingly, HIIT induced a strong increase in WAT ferritin levels independent of group. WAT ferritin levels strongly correlated with individual insulin sensitivity. Thus, we report novel proteomic signatures of WAT related to obesity and T2D and highlight an unrecognized role of human WAT iron metabolism in exercise training adaptations.
2024-01-10 | PXD040434 | Pride
Project description:Objectives Intermittent fasting is an effective dietary intervention to combat metabolic disease. Here, we explore the adipose depot specific response to every-other-day fasting (EODF) in mice to identify mechanisms that underly the beneficial effects. Methods Male C57BL/6J mice were placed on a 12-day EODF or ad libitum diet, after which tissues were harvested including visceral (vWAT) and subcutaneous (scWAT) white adipose tissue, as well as brown adipose tissue (BAT), which was then analysed by unbiased mass spectrometry-based proteomics. Results After EODF treatment, pathway enrichment analysis of our dataset showed that both WAT depots showed increased mitochondrial protein content, with scWAT also showing increased UCP1, but mitochondrial protein content was decreased in BAT. This effect on mitochondria is correlated to the increased abundance of proteins involved in glycolysis, pyruvate metabolism, the TCA cycle and fatty acid synthesis in both WAT depots. Furthermore, EODF-treated mice downregulated the lipolysis pathway in vWAT including a 5-fold decrease in the abundance of the beta3 adrenergic receptor (ADRB3). Enrichment analysis lso revealed that vWAT of EODF treated mice had significantly reduced ECM proteins, which lowers the inflammatory potential of this organ. Our adipose depot proteomic survey also allowed us to identify depot-enriched protein expression, such as the vWAT enrichment for the AKAP12 protein related to PKA signalling that was down-regulated by EODF treatment. Conclusions These findings show how the adipose depots have adapted to the EODF regime to preserve the lipid store, with the most striking changes occurring in the vWAT depot to downregulate the lipolysis pathway and induce expression of pathways needed for fatty acid synthesis. This substrate cycling and reduced inflammatory potential of the adipose tissue may contribute to the improved insulin sensitivity observed in these animals.
2022-10-12 | PXD020255 | Pride
Project description:CD44 expression has been shown to be enhanced in the liver and white adipose tissue (WAT) during obesity, suggesting a possible regulatory role for CD44 in metabolic syndrome. To study this hypothesis, we compared the gene expression profiles in liver and in WAT between WT and CD44 knockout (CD44KO) mice fed a high-fat diet (HFD) for 21 weeks. This analysis demonstrated that several genes associated with triglyceride synthesis and accumulation, including Mogat2, Cidea, Cidea, Apoa4, and Elovl7, were decreased in the livers of CD44KO mice compared to WT mice. Many genes encoding pro-inflammatory chemokines and chemokine receptors also were decreased in the livers of CD44KO mice. Analysis with WAT showed that genes associated with triglyceride accumulation, including Fasn, Elovl6 and Mogat2, were increased in WAT of CD44KO(HFD) mice compared to WT(HFD) mice. Moreover, many genes associated with inflammation, including cytokines (Cxcl14, Cxcl12, Il33, and Il2), cytokine receptors (Ccr1, Il6ra, Il10rb), trypases (Tpsb2, Tpsab1, Tpsg1), and cellular matrix proteins (Integrin ?4 (Itga4), ItgaM, Itgb2), were decreased in WAT of CD44(HFD) compared to WT(HFD) mice. This study indicates that CD44 plays a critical role in regulating several aspects of metabolic syndrome. Liver and white adipose tissue (WAT) total RNAs were purified from 5 WT and 5 CD44 knockout mice fed with a high-fat diet for 21 weeks. Then, samples were applied on Agilent mouse genome chips.
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Project description:C57BL/6 male mice were fed with normal diet or high fat diet and treated with vehicle or 30 mg/kg/day s.c. of ER-beta ligand, B-LGND2. Genes differentially expressed by H.F.D. and B-LGND2 are represented in this RNA-Sequencing data n=3/group. White adipose tissue. Mice were fed and treated as indicated above for 9 weeks. WAT was collected, RNA isolated, and expression of genes was measured by RNA-Sequencing.
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Project description:Obesity is linked to the development of metabolic disorders. Expansion of white adipose tissue (WAT) from hypertrophy of pre-existing adipocytes and/or differentiation of precursors into new mature adipocytes contributes to obesity. We found that Nck2 expression is largely restricted to WAT, raising the hypothesis that it may play a unique function in that tissue. Using mice lacking Nck2, we found that Nck2 regulates adipocyte hypertrophy thus contributing to increased adiposity and progressive glucose intolerance, insulin resistance and hepatic steatosis. These findings were recapitulated in humans such that Nck2 expression in omental WAT was inversely correlated with the degree of obesity. Mechanistically, Nck2 deficiency promoted the induction of an adipocyte differentiation program and signaling by the PERK-eIF2α-ATF4 pathway in agreement with a role for the unfolded protein response in adipogenesis. These findings uncover Nck2 as a novel regulator of adipogenesis and that perturbation in its functionality contributes to adiposity-related metabolic disorders. Differential gene expression profile between epididymal white adipose tissue of Nck2-/- and Nck2+/+ mice by RNA sequencing (Illumina HiSEq 2000)
2016-07-01 | E-GEOD-63510 | biostudies-arrayexpress