Genome-wide binding sites of Foxp4 in beige adipocyte
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ABSTRACT:
PROVIDER: PRJNA820727 | ENA |
REPOSITORIES: ENA
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Project description:We found deletion of Foxp4 in mature adipocytes would augment juvenile and mature beige adipocyte thermogenesis.In order to investage the binding site of Foxp4 in the genome of beige adipocytes, we did Foxp4 ChIP-Seq with differentiated SVF cells derived from ingunal adipose tissues.
2022-04-06 | GSE199559 | GEO
Project description:We found deletion of Foxp4 in SVF cells would inhibit beige adipocyte differentiation and thermogenesis.In order to investage the binding sites of Foxp4 on genome of SVF cells, we isolated SVF cells from ingunal adipose tissues and did Foxp4 and H3K27ac ChIP-Seqs after two days' browning differentiaion.
2022-04-06 | GSE199567 | GEO
Project description:Pharmacological activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) is a convenient and promising tactic for promoting beige adipocyte biogenesis to combat obesity-related metabolic disorders. However, thiazolidinediones (TZDs), the full agonist of PPAR-γ exhibits severe side effects in animal model and clinical uses. Therefore, it is emerging to develop efficient and safe PPAR-γ modulators for metabolic disease treatment. Here, by utilizing comprehensive methods, we report a previously unidentified ligand binding pocket (LBP) in PPAR-γ and link it to beige adipocyte differentiation. Further virtual screening from 4097 natural compounds based on this novel LBP, we discover NJT-2, a terpenoid compound, can bind to PPAR-γ induce co-activator recruitment and effectively activate PPAR-γ mediated transcription of beige adipocyte program. Importantly, in mouse model, NJT-2 administration efficiently promotes beige adipocyte biogenesis and improve obesity-associated metabolic dysfunction with significant lower adverse effects than those observed in TZD. Our results not only provide an advanced molecular insight into the structural ligand binding details in PPARg, but also develop its linked selective and safe agonist for obesity treatment.
2024-05-21 | GSE267657 | GEO
Project description:Beige adipocytes accumulates mitochondria and alleviates metabolic disorder via activating energy expenditure. Whether the opposing process of mitochondrial biogenesis and clearance are integrated regulated in beige adipocytes is beyond known. Here we show that DNA binding protein Ets1 suppresses beige adipocyte formation via bidirectional regulation of mitochondrial biogenesis and clearance. The expression level of Ets1 was down-regulated in browning adipocytes, and up-regulated in the subcutaneous fat of obese mice. Adipocyte Ets1 heterozygous knock-in mice showed suppressed beige adipocytes formation under cold stress, while the homozygous knock-in mice are cold intolerance. On the other hand, knocking out Ets1 in adipocytes enhanced energy expenditure and protect the mice from high fat diet induced metabolic disorders. Mechanical assay suggests Ets1 binds to the promoter region of mitochondria complex coding genes and autophagy related genes, transcriptionally suppresses mitochondrial biogenesis and activates its clearance. Our results indicate that Ets1 integrally regulates the balance of mitochondria generation and degradation, hence acts as a pivotal governor of mitochondria content and negatively regulates beige adipocyte formation.
2023-07-01 | GSE234879 | GEO
Project description:Molecular basis of beige adipocyte maintenance
| PRJEB11461 | ENA
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
Project description:Beige adipocytes are a distinct type of thermogenic fat cells in human. Since beige adipocytes are distributed sporadically within white adipose, characterization of human beige adipocytes has long been a problem. In this study, we reported a rapid and roboust method in generating human beige adipocyte with chemically defined medium and RNA-Seq was perfomed to reveal the molecular characterization of derived human beige adipocytes.
2020-01-01 | GSE125331 | GEO
Project description:We report that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1-alpha and prevents it from interacting with Ppar[gamma] to activate key genes, such as Ucp1, involved in beige adipocyte function.
2019-08-15 | GSE133726 | GEO
Project description:We reported that both conventional and adipose-specific Naa10p deletions in mice result in increased energy expenditure, thermogenesis, beige adipocyte differentiation and activation. Mechanistically, Naa10p acetylates the N-terminus of Pgc1α and prevents it from interacting with Ppar to activate key genes, such as Ucp1, involved in beige adipocyte function. We used microarrays to profile the gene expression changes by Naa10p KO in inguinal white adipose tissues (iWATs) derived from mice fed with high fat diet for 15 weeks.
2019-08-16 | GSE133865 | GEO
Project description:PRDM16 is an important transcriptional regulator of brown and beige adipocyte gene programs. We discovered that PRDM16 also represses type I Interferon-stimulated genes (ISGs) in brown and beige adipocytes. ChIP-seq demonstrated that PRDM16 binds proximal to many of the regulated ISGs and this correlates with reduction in the amount of the activating mark, H3K27Ac. Together this data shows PRDM16 represses ISG expression through direct binding at promoter regions to block transcription.
2017-04-10 | GSE86017 | GEO