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ABSTRACT:
PROVIDER: PRJNA547458 | ENA |
REPOSITORIES: ENA
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Project description:Ramirez2017 - Human global metabolism in
brown and white adipocytes
Recon 2.1A, an update to Recon 2.1x, is suitable for
quantitatively-realistic results for flux balance analysis in
human metabolism.
This model is described in the article:
Integrating Extracellular
Flux Measurements and Genome-Scale Modeling Reveals Differences
between Brown and White Adipocytes.
Ramirez AK, Lynes MD, Shamsi F, Xue
R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM.
Cell Rep 2017 Dec; 21(11):
3040-3048
Abstract:
White adipocytes are specialized for energy storage, whereas
brown adipocytes are specialized for energy expenditure.
Explicating this difference can help identify therapeutic
targets for obesity. A common tool to assess metabolic
differences between such cells is the Seahorse Extracellular
Flux (XF) Analyzer, which measures oxygen consumption and media
acidification in the presence of different substrates and
perturbagens. Here, we integrate the Analyzer's metabolic
profile from human white and brown adipocytes with a
genome-scale metabolic model to predict flux differences across
the metabolic map. Predictions matched experimental data for
the metabolite 4-aminobutyrate, the protein ABAT, and the
fluxes for glucose, glutamine, and palmitate. We also uncovered
a difference in how adipocytes dispose of nitrogenous waste,
with brown adipocytes secreting less ammonia and more urea than
white adipocytes. Thus, the method and software we developed
allow for broader metabolic phenotyping and provide a distinct
approach to uncovering metabolic differences.
This model is hosted on
BioModels Database
and identified by:
MODEL1703310000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1703310000 | BioModels
Project description:We performed ChIP-seq to chart genome-wide maps of H3K27me3 in brown preadipocytes and mature brown adipocytes. We observed a subset of brown fat-specific genes, but not common fat genes or white fat-specific genes, possess the H3K27me3 mark in preadipocytes, and this mark is erased in mature adipocytes. H3K27me3 ChIP-seq in brown preadipocytes and mature adipocytes.
2015-12-31 | E-GEOD-55469 | biostudies-arrayexpress
Project description:Forkhead box protein P1 (Foxp1), a transcription factor showing highly enriched expression in the striatum, has been implicated in CNS development, but its role in the mature brain is unknown. In order to ascertain functional roles for Foxp1 in the CNS, we have identified gene targets for Foxp1 in vitro using gene expression microarrays and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) assays. Transcriptome-wide analysis of Foxp1-transfected striatal cells revealed widespread expression changes of genes related to immune signaling, cancer, transcriptional regulation, and a curated Huntington’s disease (HD) signaling pathway. Integrating the microarray expression dataset with Foxp1 binding sequences determined from ChIP-seq analysis resulted in 75 direct targets of Foxp1, which included Foxp1 itself, which were also related to immune processes and the category “genetic disorder”. These findings demonstrate that Foxp1 is a primary transcriptional repressor of immunological-related gene expression in striatal cells. n=3 wt STHdh striatal cells and n=3 Foxp1-transfected STHdh striatal cells
2011-11-01 | E-GEOD-31560 | biostudies-arrayexpress
Project description:Adipocytes are key players in maintaining energy homeostasis and are classified into two different categories: white and brown adipocyte. While white adipocytes store energy as triacylglycerols in lipid droplets, brown adipocytes combust excess chemical energy and release in the form of heat through uncoupled respiration. This characteristic phenomenon of brown fat attracts researchers and pharmacological industries to view brown fat as one of the potential therapeutic targets for obesity and associated metabolic disease. In the current study, we investigated the effect of a small molecule, sesaminol (SML) on brown fat activity and found that SML induces thermogenic program in primary white adipocytes as well as chow diet fed mice. In particular, SML treatment to mice elevated mitochondrial complex proteins and the rate oxygen consumption in brown and white fat. Administration of SML to high fat diet (HFD) challenged mice decreased weight gain, adiposity and cholesterol levels along with an increase of brown fat gene program in brown and white fat. Mechanistically, SML repressed the myogenic gene program in C2C12 myoblasts and increased all mitochondrial marker genes as appeared in brown adipose cells. Together, our results demonstrate that SML stimulates brown adipose function and protects mice against diet induced weight gain.
2020-03-27 | GSE147599 | GEO
Project description:Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological ‘whitening’, but it is unknown whether or to what extent this represents a true shift in cellular identity. Using cell type-specific profiling in vivo, we uncover a unique paradigm of temperature-dependent epigenomic plasticity of beige, but not brown, adipocytes, with conversion from a brown to a white chromatin state. Despite this profound shift in cellular identity, warm whitened beige adipocytes retain an epigenomic memory of prior cold exposure defined by an array of poised enhancers that prime thermogenic genes for rapid response during a second bout of cold exposure. We further show that a transcriptional cascade involving the glucocorticoid receptor and Zfp423 can drive warm-induced whitening of beige adipocytes. These studies identify the epigenomic and transcriptional bases of an extraordinary example of cellular plasticity in response to environmental signals.
2018-03-01 | GSE108077 | GEO
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:The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands. Recent studies have demonstrated that white and brown adipocytes also function as endocrine cells and regulate systemic metabolism by secreting factors that act locally and systemically. However, a comparative proteomic analysis of secreted factors from white and brown adipocytes and their responsiveness to adrenergic stimulation has not been reported yet. Therefore, we studied and compared the secretome of white and brown adipocytes, with and without norepinephrine (NE) stimulation. Our results reveal that in the absence of NE, carbohydrate metabolism-regulating proteins are preferably secreted from white adipocytes, while brown adipocytes predominantly secrete integrin signaling proteins. Upon NE stimulation, white adipocytes secrete more proteins involved in lipid metabolism, while brown adipocytes secrete more proteins with specific anti-inflammatory properties. In conclusion, our study provides a comprehensive catalogue of novel adipokine candidates secreted from white and brown adipocytes with many of them responsive to NE.
2018-09-04 | PXD009280 | Pride
Project description:We performed ChIP-seq to chart genome-wide maps of H3K27me3 in brown preadipocytes and mature brown adipocytes. We observed a subset of brown fat-specific genes, but not common fat genes or white fat-specific genes, possess the H3K27me3 mark in preadipocytes, and this mark is erased in mature adipocytes.
2015-12-31 | GSE55469 | GEO
Project description:Classical brown adipocytes in interscapular BAT (Myf-5 derived) and inducible beige cells in WAT (non-Myf-5 derived) have distinct developmental origins, although both cell types have morphological and biochemical characteristics of brown fat such as the expression of UCP1. This raises an important question as to how similar the two types of brown adipocytes are at molecular and functional levels. To this end, we employed RNA-seq to systematically determine the transcriptional signatures unique to each cell type.
2015-03-16 | E-MTAB-2624 | biostudies-arrayexpress
Project description:To study the role of Ybx2 in brown fat activity, we performed the RNA-seq data for wildtype and Ybx2 knockout brown fat under room temperature and upon cold exposure as well as for wildtype and Ybx2 knockout brown adipocytes culture from stromal vascular fraction cells. To determine the targets of Ybx2, we performed RNA immunopercipitatoin followed by RNA-seq
2019-08-23 | GSE86590 | GEO