A subpopulation of lipogenic brown adipocytes drives thermogenic memory
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA905100 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22404877.fastq.gz | Fastqsanger.gz | |||
| SRR22404878.fastq.gz | Fastqsanger.gz | |||
| SRR22404879.fastq.gz | Fastqsanger.gz | |||
| SRR22404880.fastq.gz | Fastqsanger.gz | |||
| SRR22404881.fastq.gz | Fastqsanger.gz |
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Project description:Sustained responses to transient stimuli are important for animals to survive and reproduce in their environment. However, the mechanisms that underlie altered responses to temporary shifts in abiotic factors, such as temperature, remain poorly understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which are critical for an improved thermogenic response to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis program even after cessation of the original stimulus, which protects from subsequent exposures. By combining single-nucleus RNA sequencing, spatial transcriptomics, and immunofluorescence imaging, we discover that this lipogenic response is carried out by a distinct subpopulation of brown adipocytes that is localized along the perimeter of classical Ucp1high brown adipocytes. The protective effect of the lipogenic program is associated with the production of acyl carnitines, and supplementation of acyl carnitines recapitulates improved secondary cold responses even in the absence of lipogenesis. Overall, our data highlight the importance of heterogenous brown adipocyte populations for “thermogenic memory” in the setting of repeated cold exposure, which may have implications for therapeutic efforts leveraging short-term thermogenesis to counteract the hypercaloric state of obesity.
2023-09-11 | GSE218709 | GEO
Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory [snRNAseq]
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Project description:A subpopulation of lipogenic brown adipocytes drives thermogenic memory [Spatial Transcriptomics]
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Project description:Spatial transcriptomics of brown adipose tissue from thermoneutrality (TN) and from mouse that had undergone transient acute cold exposure 4 days previously (1cyc)
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Project description:Brown adipose tissue (BAT) generates heat via uncoupled respiration, providing mammals with an evolutionary defense against environmental cold. Although the molecular pathways by which cold activates brown adipocytes are well understood, little is known about how BAT maintains its thermogenic capacity during adaptation to environmental warmth. Here, we identify the transcriptional repressor BCL6 as the switch for maintaining brown adipocyte cellular identity under warm conditions. Mice lacking BCL6 in their brown adipocytes display normal thermogenic responses when housed in a cool environment, but fail to maintain thermogenic fitness when housed under warm conditions. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic competence in brown adipocytes. Enhancer analysis revealed that BCL6 reinforces brown-specific while opposing white-specific enhancers to maintain cellular identity. Thus, unlike other regulators, BCL6 is dispensable for differentiation and activation of brown adipocytes, but specifically required for their maintenance in warmth.
2019-08-29 | GSE122746 | GEO
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
Project description:Brown adipose tissue (BAT) dissipates energy and promotes cardio-metabolic health4. However, loss of BAT during obesity and aging is a principal hurdle for BAT-centered obesity therapies. So far not much is known about BAT apoptosis and signals released by apoptotic brown adipocytes. Here, untargeted metabolomics demonstrated that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched. Interestingly, this apoptotic secretome enhances expression of the thermogenic program in healthy adipocytes to maintain tissue functionality. This effect is mediated by the purine inosine which stimulates energy expenditure (EE) in brown adipocytes. Phosphoproteomic analysis demonstrated activation of the cAMP/protein kinase A signaling pathway and of pro-thermogenic transcription factors by inosine.
2022-05-31 | PXD032153 | Pride
Project description:Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure (EE) and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show by phosphoproteomics that cAMP activates distinct signaling pathways in brown progenitors, with the cAMP-EPAC1 axis enhancing proliferation and differentiation of thermogenic but not white adipocytes. Further analysis revealed that a specific subpopulation of preadipocytes that are PDGFRα-positive express EPAC1. In vivo, pharmacological activation of EPAC1 enhances BAT growth and browning of white fat, leading to increased EE and reduced diet-induced adiposity. In contrast, mice lacking EPAC1 in PDGFRα-positive preadipocytes show the opposite phenotype. Importantly, EPAC1 activation enhances proliferation and differentiation of human brown adipocytes and human brown fat organoids. Interestingly, a coding variant in EPAC1 that positively correlates with BMI abolishes norepinephrine-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and EE to combat metabolic diseases.
2023-11-11 | PXD046709 | Pride
Project description:Purpose: To test if there is a heterogeneity within brown adipocytes, we performed single cell RNA-sequencing of primary brown adipocytes isolated from mouse brown adipose tissue. Methods: Brown adipocytes from 10-week-old C57BL/6J male mice were freshly collected and resuspended in PBS containing 0.04% BSA at a concentration of 700~1200 cells/µl. Cell number and viability were measured using a TC20 Automated Cell Counter (BioRad). Single-cell RNA libraries were prepared according to the Chromium™ Single Cell 3' Reagent Kits v2 User Guide (10x Genomics). Approximately 10,000 cells were loaded on a Chromium single cell Controller instrument (10x Genomics) to generate single cell gel beads in emulsion (GEMs). The barcoded sequencing libraries were constructed using the Chromium Single-Cell 3′ Library Kit (10x Genomics) for enzymatic fragmentation, end-repair, A-tailing, adaptor ligation, ligation cleanup, sample index PCR, and PCR cleanup. Libraries were sequenced with a Hiseq 2500 instrument (Illumina) with a depth of 50k-100k reads per cell. Raw sequencing data were processed using the 10x Genomics Cell Ranger pipeline (version 2.0) to generate FASTQ files and aligned to mm10 genome to gene expression count. The subsequent data analysis was performed using “Seurat” package and R scripts. Cells with mitochondrial read rate > 50% and < 200 detectable genes were considered as low-quality and filtered out. Normalized and scaled data were clustered using the top significant principal components of highly variable genes. The t-distributed stochastic neighbor embedding (t-SNE) algorithm was used to visualize the resulting clusters. Cluster-specific markers were identified to generate heatmap and feature plots in the identified cell clusters. Genes were compared between different clusters using Bioconductor package “Limma” on normalized data. Gene Set Enrichment Analysis (GSEA) v3 was performed using genes ranked by the fold changes between different clusters to evaluate the significant activation of the C2 KEGG gene sets in MSigDb (http://software.broadinstitute.org/gsea/msigdb/collections.jsp). Results: Two major brown adipocyte subpopulations were clustered as brown adipocytes with high thermogenic activity (BA-H, 2,352 cells) and brown adipocytes with low thermogenic activity (BA-L, 1,250 cells). Conclusions: In summary, the brown adipocyte single cell transcriptomic reveals a unique subpopulation of brown adipocytes with low thermogenic activity. These cells hold a unique metabolic status, and the function of these cells is fundamentally different from the cells within the BA-H subpopulation.
2019-12-10 | GSE125269 | GEO