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CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE242244 | GEO | 2026/03/20

REPOSITORIES: GEO

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

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 | GSE245346 | GEO

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

2026-03-20 | GSE242243 | GEO

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

2026-03-20 | GSE242242 | GEO

CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2

Project description:CarS2 mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2

| PRJNA1012485 | ENA

CarS2-mediated cysteine catabolism drives brown fat development and thermogenesis through persulfidating EBF2

Project description:Targeting transcriptional regulatory complexes is a promising strategy to activate thermogenic fat and treat obesity. In this study, we focused on identifying critical and specific 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 highly increased in brown adipocyte differentiation. Then, we demonstrated cysteine persulfidation synthase CarS2 is directly induced by EBF2, mediates cysteine catabolism and triggers brown fat protein persulfidation both in vitro and in vivo. Loss of CarS2 in thermogenic fat blocks brown fat formation in both male and female mice, and CarS2 depletion in mice reduces thermogenesis and energy expenditure. More importantly, CarS2 generates cysteine persulfide, and its derivative H2S cell-autonomously induces brown adipogenesis and enhances uncoupled respiration by persulfidating EBF2. Mechanistically, persulfidated EBF2 facilitates its interaction with PPARγ or BRG1, enhancing the recruitment of the EBF2-PPARγ complex to the browning gene promoter, thus driving brown fat development and boosting thermogenic activity. Furthermore, treatment with 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 obesity treatment.

2026-03-24 | MTBLS12234 | MetaboLights

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

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

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Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2.

Project description:Targeting transcriptional regulatory complexes represents a promising strategy for activating thermogenic fat and treating obesity. In this study, we focused on identifying critical, specific metabolic pathways enriched during brown adipocyte differentiation. Through analysis of metabolomics and RNA sequencing data from precursor and mature brown and white adipocytes, we revealed that the cysteine catabolism pathway constitutes a unique metabolic process that is significantly upregulated during brown adipocyte differentiation. We further demonstrated that the cysteine persulfidation synthase Cars2, which is directly induced by EBF2, mediates cysteine catabolism and triggers brown fat protein persulfidation both in vitro and in vivo. Loss of Cars2 in thermogenic fat blocks brown fat formation, resulting in mice exhibiting reduced thermogenesis and energy expenditure. More importantly, Cars2 generates cysteine persulfide and its derivative H<sub>2</sub>S cell-autonomously induces brown adipogenesis and enhances uncoupled respiration through persulfidation of EBF2. Mechanistically, persulfidated EBF2 facilitates its interaction with PPARγ or BRG1, enhancing recruitment of the EBF2-PPARγ complex to browning gene promoters, thereby driving brown fat development and boosting thermogenic activity. Furthermore, treatment with the Cars2 coenzyme PLP or an H<sub>2</sub>S donor enhances brown adipocyte function and alleviates obesity progression in mice fed a high-fat diet, indicating a novel metabolite-based strategy for obesity treatment.

2026-03-24 | MTBLS12237 | MetaboLights

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

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

| PRJNA1012488 | ENA

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

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

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