Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome comparison of white adipose tissue between control and adipose specific HuR knockout mice

ABSTRACT: Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL), a critical lipase involved in lipolysis. HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans, which is associated with reduced ATGL expression. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.

ORGANISM(S): Mus musculus

PROVIDER: GSE130147 | GEO | 2019/04/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Adipose METTL14-elicited N6-methyladenosine promotes obesity, insulin resistance, and NAFLD by suppressing β adrenergic signaling and lipolysis

Project description:Obesity is associated with impaired β-adrenergic receptor (Adrb1-3) signaling and lipolysis, leading to aberrant white adipose tissue (WAT) growth. WAT research has been centered on transcriptional and posttranslational regulations, but posttranscriptional regulation and mRNA modifications are poorly understood. Here, we unveil a METTL14/N6-methyladenosine (m6A) paradigm guiding β-adrenergic signaling and lipolysis. METTL14 complex installs m6A on RNA, regulating mRNA fate and translation. We found that feeding and insulin increased adipose Mettl14 and m6A levels. Adipose Mettl14 and m6A were upregulated in high fat diet (HFD)-induced obesity. Ablation of adipose Mettl14 decreased Adrb2, Adrb3, Atgl (encoding lipase), and Cig-58 (Atgl activator) transcript m6A contents while increasing their translation and protein levels, thereby enhancing adipose β-adrenergic signaling and lipolysis. Consequently, adipocyte-specific Mettl14 knockout mice were resistant to HFD-induced obesity, insulin resistance, glucose intolerance, and NAFLD. These results unravel a METTL14/m6A-based epitranscriptomic mechanism governing β-adrenergic signaling, lipolysis, and adipose growth in health and disease.

2023-06-04 | GSE233782 | GEO

Expression data from cultured mouse macrophages isolated from Hilpdaflox/flox (WT) and HilpdaΔMΦ (KO) mice treated with a mixture of fatty acids

Project description:Obesity leads to a state of chronic low-grade inflammation that features accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid droplet accumulation in the development of obesity-induced adipose tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently-labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages could be rescued by inhibition of adipose triglyceride lipase (ATGL) and was associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency did not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-induced physiological inhibitor of ATGL-mediated lipolysis in macrophages that uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.

2019-12-19 | GSE142295 | GEO

Mouse peritoneal macrophages treated with three different fatty acids

2019-12-19 | GSE142294 | GEO

Protein kinase A phosphorylation of perilipin 5 on serine 155 regulates liver lipolysis via interactions with adipose triglyceride lipase

Project description:Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, a-b hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but this was not associated with changes in other parameters of hepatic lipid metabolism. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A when compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism.

2021-03-11 | PXD021969 | Pride

Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue.

Project description:Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.

2024-04-23 | PXD048506 | Pride

Loss of adipose triglyceride lipase aids cancer growth in 3D

Project description:Shotgun proteomic analysis of 3D-grown or on CAM-assay grown lung cancer cells lacking or expressing the major triglyceride lipase adipose triglyceride lipase (ATGL)

2021-05-21 | PXD021105 | Pride

Effects of short-term starvation on the transcriptome and lipid metabolism of epididymal white adipose tissue in mice

Project description:Beneficial effects have been reported in individuals undergoing fasting to treat excessive weight gain and obesity. To better understand the effects of starvation on the transcriptome and lipid metabolism of white adipose tissue, we established a mouse model of 24-hour fasting using wild type C57BL/6J mice, and performed RNA-seq analysis of the white adipose tissue from the epididymis of fasted mice and control mice. Compared with the control fed mice, these fasted mice showed suppressed lipid synthesis and inhibited insulin signaling, while the lipolysis and gluconeogenesis were enhanced to maintain blood sugar stability. Specifically, the fasted mice had reduced volume of adipose tissues, increased levels of serum NEFA and ANP. In epididymal white adipose tissue, starvation increased the NEFA content, up-regulated the mRNA levels of Atgl, Adrb2, Anp, and Npr1, and promoted the phosphorylation of Hsl. Notably, bioinformatics analysis of the RNA-seq data showed that 24-hour fasting-induced alterations in lipid metabolism was associated with suppressed AMPK signaling and enhanced PPAR signaling in white adipose tissue, which was verified by quantitative PCR. Collectively, these findings supported that starvation promoted the conversion of energy-supplying substrates from glucose to fat. Our work sheds new light on harnessing the plasticity of adipose tissues and the AMPK/PPAR signaling pathways to develop potential strategies to combat obesity and other glucose/lipid metabolisms-associated human diseases.

2022-10-01 | GSE207913 | GEO

Lipolysis Engages CD36 to Promote ZBP1-Mediated Necrosis Impairing Lung Regeneration in COPD

Project description:Lung parenchyma destruction represents a severe condition commonly found in chronic obstructive pulmonary disease (COPD), the leading cause of morbidity and mortality worldwide. Promoting lung regeneration is crucial for achieving clinical improvement. However, no therapeutic drugs are approved to improve the regeneration capacity due to incomplete understanding of the underlying pathogenic mechanisms. Here, we identify a positive feedback loop formed between adipose triglyceride lipase (ATGL)-mediated lipolysis and overexpression of CD36 specific to lung epithelial cells, contributing to disease progression. Genetic deletion of CD36 in lung epithelial cells and pharmacological inhibition of either ATGL or CD36 effectively reduce COPD pathogenesis and promote lung regeneration in mice. Mechanistically, disruption of the ATGL-CD36 loop rescued Z-DNA binding protein 1 (ZBP1)-induced cell necroptosis and restored WNT/β-catenin signaling. Thus, we uncover a previously unrecognized crosstalk between lipolysis and lung epithelial cells, suggesting the regenerative potential for therapeutic intervention by targeting the ATGL-CD36-ZBP1 axis in COPD.

2024-12-13 | GSE246501 | GEO

Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity

Project description:Obesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role of adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LDs) utilization, in obesity driven colonic tumorigenesis. In local colon cancer patients, significantly increased ATGL levels in tumor tissue, compared to controls, were augmented in obese individuals. Elevated ATGL levels in human colon cancer cells (CCC) relative to non-transformed were augmented by an obesity mediator, oleic acid (OA). In CCC and colonospheres, enriched in colon cancer stem cells (CCSC), inhibition of ATGL prevented LDs utilization and inhibited OA-stimulated growth through retinoblastoma-mediated cell-cycle arrest. Further, transcriptomic analysis of CCC, with inhibited ATGL, revealed targeted pathways driving tumorigenesis and high-fat-diet obesity facilitated tumorigenic pathways. Inhibition of ATGL in colonospheres revealed targeted pathways in human colonic tumor crypt base cells (enriched in CCSC) derived from colon cancer patients. In CCC and colonospheres, we validated selected transcripts targeted by ATGL inhibition, some with emerging roles in colonic tumorigeneses (ATG2B, PCK2, PGAM1, SPTLC2, IGFBP1, ABCC3) and others with established roles (MYC, MUC2). These findings demonstrate obesity-promoted, ATGL-mediated colonic tumorigenesis and establishes therapeutic significance of ATGL in obesity reinforced colon cancer progression.

2022-02-05 | GSE195994 | GEO

Obesity expands a distinct population of adipose-resident T cells and increases vulnerability to infection

Project description:Obesity in humans is associated with worsened health outcomes following infections compared to non-obese individuals. Here, we examined the effects of adipose tissue and obesity on T cell responses to virus infection in mice. Lymphocytic choriomeningitis virus (LCMV) grew to high titer in adipose tissue. Virus-specific T cells enter the adipose tissue to resolve infection but then remain as a memory population distinct from memory T cells in lymphoid tissues. Memory CD4+ and CD8+ T cells residing in adipose were abundant, accounting for roughly 10% of all virus-specific memory T cells. Diet-induced obesity increased memory T cell number in adipose and spleen. Upon re-challenge infection, memory T cells caused severe pathogenesis, leading to sharply increased lipase levels, calcification of adipose tissue, pancreatitis, and reduced survival in obese mice but not lean mice. Thus, obesity leads to a unique form of viral pathogenesis involving memory T cell-dependent adipocyte destruction and collateral damage to other tissues.

2019-03-19 | GSE110212 | 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