Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPβ

ABSTRACT: The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT), however, knowledge of the intracellular determinants of browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we showed that SENP2 negatively regulates browning by de-conjugating SUMO from C/EBPβ. Senp2-aKO mice were resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and heat production. Senp2 knockout promoted beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promoted thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppressed expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.

ORGANISM(S): Mus musculus

PROVIDER: GSE189326 | GEO | 2023/11/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

SENP2 suppresses browning of white adipose tissues by de-conjugating SUMO from C/EBPβ

Project description:The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT), however, knowledge of the intracellular determinants of browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we showed that SENP2 negatively regulates browning by de-conjugating SUMO from C/EBPβ. Senp2-aKO mice were resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and heat production. Senp2 knockout promoted beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promoted thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppressed expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.

2023-11-27 | GSE189387 | GEO

Adipose tissue from β-3 agonist-treated mice

Project description:We previously established the transcription factor Zfp423 is critical for maintaining white adipocyte identity through suppression of the thermogenic gene program. The loss of Zfp423 in mature adipocytes triggers the rapid conversion of energy-storing white adipocytes into thermogenic beige adipocytes in subcutaneous WAT. In contrast to subcutaneous WAT, visceral WAT is relatively resistant to browning. However, visceral adipocytes lacing Zfp423 are capable of inducing the thermogenic gene program upon β-3 adrenergic stimulus. Here, we generated mice lacking Zfp423 in visceral adipose by breeding transgenic mice expressing Cre recombinase under the control of the Wilms Tumor 1 locus (Wt1-Cre) to animals carrying the floxed Zfp423 alleles (Zfp423loxP/loxP) (“Vis-KO” mice). Inactivation of Zfp423 in visceral WAT gives rise to thermogenic adipocytes that share properties of subcutaneous beige adipocytes and classic brown adipocytes.

2017-04-25 | GSE98132 | GEO

ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChIP-seq

Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.

2022-05-01 | GSE175654 | GEO

ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChAP-seq

2022-05-01 | GSE175653 | GEO

A non-cell autonomous mechanism of beige adipocyte renaissance in subcutaneous adipose tissue

Project description:Two types of UCP1 positive cells-brown and beige adipocytes exist in mammals. Beige adipocytes are very plastic, and can be dynamically regulated by environment.Beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold could restore their “beigeing” characteristics, a phenomenon termed as beige adipocyte renaissance. Our results showed that beige cell maintenance and renaissance in adult mice were regulated by cAMP and HDAC4 signaling in white adipocytes non-cell autonomously. Genetic modulations of various components of this cAMP-HDAC4 cascade (e.g. LKB1) led to persistent browning and reduced adiposity independent of thermogenesis. To further study the mechanisms of beige adipocytes maintenance, we performed RNA-seq with samples from inguinal white adipose tissues of WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice.Our studies will move the beige adipocyte field forward and attract clinical applications to target beige adipocyte renaissance.

2018-02-14 | GSE85335 | GEO

LncRNAs expression profiling in adipose tissues and during brown adipocyte differentiation

Project description:Brown and beige fats generate heat via uncoupled respiration to defend against cold, mechanistically, through the action of a network of transcription factors and cofactors. Here we globally profiled long noncoding RNAs (lncRNAs) gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function by forming a feedforward regulatory loop with EBF2 to drive adipogenesis toward thermogenic phenotype. LncRNAs expression were measured in BAT and WAT from mice injected saline/CL and during brown adipocyte differentiation with two replicates using Arraystar Mouse LncRNA microarray V2.0

2015-02-28 | E-GEOD-57643 | biostudies-arrayexpress

Single Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis

Project description:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWAT). Both cold- and iAdFASNKO-induced iWAT “browning” pathways upregulate the sympathetic nerve fiber (SNF) modulator Nrg4 and activate SNFs adjacent to beige adipocytes. Adipocyte cAMP/protein kinase A signaling is necessary for beige adipocyte appearance, as we show here it is blocked in Gsa deficient cold exposed or iAdFASNKO mice. Surprisingly however, denervation of iWAT failed to block adipocyte browning in iAdFASNKO mice, as it does in cold-exposed mice. Similarly, Nrg4 deficiency markedly reduced iWAT UCP1 in the cold, but not in double FASN/Nrg4 KO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type in iAdFASNKO mice, and their depletion abrogated iWAT beiging. Altogether, these findings reveal divergent cellular pathways are sufficient to cause adipocyte browning. Importantly, adipocyte signaling to enhance alternatively activated macrophages in iAdFASNKO mice is associated with enhanced adipose thermogenesis independent of the sympathetic neuron involvement this process requires in the cold.

2020-08-18 | GSE154047 | GEO

RNAseq analysis of adipose tissue transcriptomes from wild-type and FNIP1 adipocyte specific knockout (FNIP1-AKO) mice

Project description:Activation of thermogenesis in brown and beige adipocytes upon activation by external stimuli burns fuel energy as heat. Owing to its remarkable benefits on metabolic health and its demonstrated presence in adult humans, beige adipocytes holds great promise to combat obesity and metabolic diseases. Folliculin interacting protein 1 (FNIP1) is an adaptor protein originally identified through its interaction with folliculin (FLCN) and AMPK. To investigate the physiological role of FNIP1 in adipose tissue in vivo, we generated adipocyte-specific FNIP1 deficient mice (referred to as FNIP1-AKO) by crossing mice bearing a conditional Fnip1 allele with introns 5 and 6 floxed (Fnip1 lox/lox) with the adiponectin promoter–driven Cre mice. We performed transcriptome analysis by whole-genome gene expression profiling experiments in inguinal white adipose tissue (iWAT) from both wild-type (WT) and FNIP1-AKO mice. We were particularly interested in the subset of genes that were up-regulated in the FNIP1-AKO mice. Gene ontology (GO) analysis revealed that the primary up-regulated genes were mitochondrial and lipid metabolism-related genes. Gene expression validation studies demonstrated that a broad array of genes involved in thermogenic and mitochondrial oxidative program was induced in FNIP1-AKO iWAT. Together, the transcriptional profiling results indicate that loss of FNIP1 activate thermogenic program in white adipocytes.

2022-02-26 | GSE185067 | GEO

Genome-wide mapping of H3K4me1 status in primary adipocytes isolated from wild-type (WT) and Lonp1-knockout (LONP1 AKO) mice

Project description:Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity acting both as protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. It remains unclear, however, whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switch such as white-to-beige conversion of adipocytes. We found that disruption of LONP1-dependent proteolysis substantially impairs thermogenic molecular program and cellular respiration in in vitro differentiated primary adipocytes. qPCR analysis showed that expression levels of Ucp1 and other beige adipocyte thermogenic genes were remarkably downregulated in LONP1 AKO adipocytes. We took a deeper dive into the characterization of histone modifications in LONP1 AKO adipocytes using the global enhancer marker H3K4me1 ChIP-Seq. These unbiased ChIP seq data are strong evidence of that LONP1 loss results in decreased H3K4me1 on a broad array of thermogenic genes. These results collectively indicate that LONP1 is crucial to maintain proper epigenetic homeostasis and beige thermogenic gene expression.

2023-04-08 | GSE222490 | GEO

Cold-Responsive DPP4+ Progenitor Cells Facilitate Thermogenic Remodeling of Subcutaneous Adipose Tissue_p-CREB ChIP seq

Project description:The physiological adaptation to cold environmental temperatures involves the remodeling of energy-storing white adipose tissue (WAT) into an energy-burning thermogenic phenotype, characterized by the emergence of multi-locular beige adipocytes. To date, the full array of cold-responsive cells within WAT that mediate thermogenic remodeling remain undefined. Here, we demonstrate that distinct perivascular PDGFRb+ adipocyte precursor cell (APC) subpopulations are differentially sensitive to cold temperatures in vivo. One day of cold exposure elicits striking transcriptional changes in DPP4+ PDGFRb+ APCs, whereas committed DPP4- PDGFRb+ preadipocytes appear comparatively much less responsive. This adaptation includes beta-adrenergic receptor mediated induction in the expression of the pro-thermogenic cytokine, IL-33. DPP4+ PDGFRb+ cells represent the sole source of IL-33 within inguinal WAT of adult mice. Doxycycline-inducible deletion of Il33 in PDGFRb+ cells at the onset of cold exposure significantly compromises the thermogenic remodeling of WAT without directly impacting the differentiation capacity of APCs per se. Together, these studies reveal the presence of a cold-responsive progenitor cell subpopulation in adult WAT and highlight their ability to regulate tissue plasticity through the production of immunological factors.

2021-11-09 | GSE169669 | 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