Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA260210 | ENA |
REPOSITORIES: ENA
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Project description:Human brown fat tumors (hibernomas) display concomitant loss of the tumor suppressor genes MEN1 and AIP. In the present study, we hypothesized that the brown fat phenotype is attributed to these mutations. Accordingly, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumors, loss of MEN1 was found both in white (one out of 51 lipomas) and brown fat tumors. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumors is mediated by the loss of AIP.
2017-08-10 | GSE61093 | GEO
Project description:Hibernomas are benign tumors with morphological features resembling brown fat. They consistently display cytogenetic rearrangements, typically translocations, involving chromosome band 11q13. Here we demonstrate that these aberrations are associated with concomitant deletions of AIP and MEN1, tumor suppressor genes that are located 3 Mb apart and that underlie the hereditary syndromes pituitary adenoma predisposition and multiple endocrine neoplasia type I. MEN1 and AIP displayed a low expression in hibernomas whereas the expression of genes up-regulated in brown fat-PPARA, PPARG, PPARGC1A, and UCP1-was high. Thus, loss of MEN1 and AIP is likely to be pathogenetically essential for hibernoma development. Simultaneous loss of two tumor suppressor genes has not previously been shown to result from a neoplasia-associated translocation. Furthermore, in contrast to the prevailing assumption that benign tumors harbor relatively few genetic aberrations, the present analyses demonstrate that a considerable number of chromosome breaks are involved in the pathogenesis of hibernoma. Global copy number analysis was performed using single nucleotide polymorphism (SNP) array. Cases 1-14 were hybridized onto Illumina Human1M-Duo v3.0 (and Human CNV370-Quad v3.0) BeadChip (Illumina, San Diego, CA, USA), following standard protocols supplied by the manufacturer. Case 15 was analyzed using Illumina Human Omni-Quad BeadChip. Normal blood DNA was analyzed in cases 1, 2, 4 and 6 using the Human CNV370-Quad v3.0 BeadChip. Data analysis was done using the BeadStudio software (Illumina).
2010-11-24 | E-GEOD-19040 | biostudies-arrayexpress
Project description:Hibernomas are benign tumors with morphological features resembling brown fat. They consistently display cytogenetic rearrangements, typically translocations, involving chromosome band 11q13. Here we demonstrate that these aberrations are associated with concomitant deletions of AIP and MEN1, tumor suppressor genes that are located 3 Mb apart and that underlie the hereditary syndromes pituitary adenoma predisposition and multiple endocrine neoplasia type I. MEN1 and AIP displayed a low expression in hibernomas whereas the expression of genes up-regulated in brown fat-PPARA, PPARG, PPARGC1A, and UCP1-was high. Thus, loss of MEN1 and AIP is likely to be pathogenetically essential for hibernoma development. Simultaneous loss of two tumor suppressor genes has not previously been shown to result from a neoplasia-associated translocation. Furthermore, in contrast to the prevailing assumption that benign tumors harbor relatively few genetic aberrations, the present analyses demonstrate that a considerable number of chromosome breaks are involved in the pathogenesis of hibernoma.
2010-11-24 | GSE19040 | GEO
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
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
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
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 | GSE242243 | GEO
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
Project description:Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for obesity and its associated metabolic disorders. To provide a comprehensive picture of the regulatory network in these processes, we conducted a series of transcriptome studies by RNA-seq and quantified the mRNA and lncRNA changes during white fat browning induced by chronic cold exposure, beta-adrenergic agonist and intensive exercises, brown fat activation by acute cold exposure and inactivation by thermoneutrality.
2017-08-01 | GSE86338 | GEO
Project description:Activation and recruitment of thermogenic cells in human white adipose tissues (“browning”) can counteract obesity and associated metabolic disorders. However, quantifying the effects of therapeutic interventions on browning remains enigmatic. Here, we devise a computational approach, profiling of fat tissue types (ProFAT), for the quantification of thermogenic potential of heterogeneous fat biopsies based on the prediction of white and brown adipocytes content from raw gene expression profiles. ProFat systematically integrates 103 mouse fat-derived transcriptomes to identify unbiased and robust gene signatures of brown and white adipocytes. Application of ProFAT to 80 mouse and 97 human transcriptional profiles from 14 independent studies correctly predicts browning capacity upon various physiological and pharmacological stimuli. Our study represents the most exhaustive comparative analysis of public data on adipose biology towards quantification of browning after personalized medical intervention. ProFat is freely available and should become increasingly powerful with the growing wealth of transcriptomics data.
2018-04-02 | GSE112582 | GEO