Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2 [Cut & Tag]

ABSTRACT: Targeting transcriptional regulatory complex is a promising strategy to activate thermogenic fat and treat obesity. In this study, we focus on identifying critical and special metabolic pathways enriched during brown adipocyte differentiation. By analyzing metabolomics and RNA sequencing results from precursor and mature brown and white adipocytes, we revealed cysteine catabolism pathway is a unique metabolic process that is exclusively increased in the brown adipocyte differentiation. Then, we demonstrated cysteine persulfidation synthase CarS2 is directly induced by EBF2 and mediates cysteine catabolism to produce cysteine persulfide and triggers brown fat protein persulfidation in vitro and in vivo. Loss of CarS2 in thermogenic fat blocks brown and beige fat formation and reduced thermogenesis and energy expenditure in mice. More importantly, CarS2 generates cysteine persulfide and its derivative H2S cell autonomously induces brown adipogenesis and enhances uncoupled respiration by persulfidating EBF2. Mechanistically, the persulfidated EBF2 facilitates its interaction with PPARγ and enhanced the recruitment of the EBF2-PPARγ complex on browning gene promoter, thus driving brown fat development and boosting thermogenic function. Furthermore, the treatment of CarS2 coenzyme PLP or H2S donor elevates brown adipocyte function and ameliorates obesity progression in mice under HFD feeding, indicating a novel metabolite-based strategy for the obesity treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE245346 | GEO | 2026/03/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2 [AKO and wt Acute cold]

Project description:Targeting transcriptional regulatory complex is a promising strategy to activate thermogenic fat and treat obesity. In this study, we focus on identifying critical and special metabolic pathways enriched during brown adipocyte differentiation. By analyzing metabolomics and RNA sequencing results from precursor and mature brown and white adipocytes, we revealed cysteine catabolism pathway is a unique metabolic process that is exclusively increased in the brown adipocyte differentiation. Then, we demonstrated cysteine persulfidation synthase CarS2 is directly induced by EBF2 and mediates cysteine catabolism to produce cysteine persulfide and triggers brown fat protein persulfidation in vitro and in vivo. Loss of CarS2 in thermogenic fat blocks brown and beige fat formation and reduced thermogenesis and energy expenditure in mice. More importantly, CarS2 generates cysteine persulfide and its derivative H2S cell autonomously induces brown adipogenesis and enhances uncoupled respiration by persulfidating EBF2. Mechanistically, the persulfidated EBF2 facilitates its interaction with PPARγ and enhanced the recruitment of the EBF2-PPARγ complex on browning gene promoter, thus driving brown fat development and boosting thermogenic function. Furthermore, the treatment of CarS2 coenzyme PLP or H2S donor elevates brown adipocyte function and ameliorates obesity progression in mice under HFD feeding, indicating a novel metabolite-based strategy for the obesity treatment.

2026-03-20 | GSE242242 | GEO

CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2 [BAC and L1 differ]

2026-03-20 | GSE242243 | GEO

Vector and Brown fat lncRNA 1 (Blnc1) expressing differentiated brown adipocytes

Project description:Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and the induction of the thermogenic gene program. Brown adipocytes expressing vector or brown fat lncRNA 1 (blnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.

2015-02-28 | E-GEOD-55551 | biostudies-arrayexpress

Scramble and Brown fat lncRNA 1 knockdown (shBlnc1) expressing differentiated brown adipocyte

Project description:Blnc1 is a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function. Blnc1 forms a ribonucleoprotein complex with transcription factor EBF2 to stimulate the thermogenic gene program. Further, Blnc1 itself is a target of EBF2, thereby forming a feedforward regulatory loop to drive adipogenesis toward thermogenic phenotype. We used microarrays to elucidate the role of Blnc1 on brown adipocyte differentiation and mitochondrial function. Brown adipocytes expressing Scramble or brown fat lncRNA 1 knockdown (shBlnc1) were differentiated for 6 days and harvested for RNA isolation and microarray using Affymetrix Mouse MG-430 PM Strip arrays. Two replicated samples were included in this study.

2015-02-28 | E-GEOD-57540 | biostudies-arrayexpress

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

LncRNAs expression profiling in adipose tissues and during brown adipocyte differentiation

2015-02-28 | GSE57643 | GEO

Targeting EBF2 condensates modulates adipose thermogenesis

Project description:Brown adipose tissue (BAT) actively dissipates energy and represents a promising therapeutic target for combating obesity. The establishment of the thermogenic gene program is orchestrated by the pioneering transcription factor Early B Cell Factor 2 (EBF2). Here, we identified a low-complexity C-terminal domain (CTD) within EBF2 that drives biomolecular condensation and is essential for thermogenic activation. Deletion of the CTD (EBF2 ΔCTD) or mutation of key proline residues within this region did not affect the genomic binding of EBF2, but profoundly impaired its ability to undergo phase separation and to drive brown adipocyte differentiation and thermogenic function both in vitro and in vivo. Fusion of the intrinsic disorder region (IDR) of FUS to EBF2 ΔCTD fully restored its function, whereas fusion with MED1-IDR resulted in distinct phenotypic outcomes. Mechanistically, EBF2 formed condensates with ZFP423, a key repressor of brown adipocyte differentiation. This co-condensation excluded HDAC1 from the complex, establishing a permissive chromatin environment that promotes active transcription. Furthermore, a phase separation-based phenotypic drug screen identified compounds that modulated EBF2 condensate formation and thermogenic genes expression. Our findings reveal phase separation as an emerging regulatory mechanism underlying brown fat determination and suggest that targeting biomolecular condensation offers a novel therapeutic strategy for obesity.

2026-03-11 | GSE297178 | GEO

Vector and Brown fat lncRNA 1 (Blnc1) expressing differentiated brown adipocytes

2015-02-28 | GSE55551 | GEO

Scramble and Brown fat lncRNA 1 knockdown (shBlnc1) expressing differentiated brown adipocyte

2015-02-28 | GSE57540 | GEO

ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChAP-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 | GSE175653 | 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