Gene expression of BAT from GRBATKO mice exposed to cold
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE135544 | GEO | 2019/08/26
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic stressors flatten circadian glucocorticoid (GC) oscillations, which has been correlated with negative health outcomes including obesity. How such flattened circadian GC oscillations affect metabolism and fat storage remains unknown. Here we investigated the consequences in mice and found that flattening of GC oscillations results not only in body weight gain, mainly due to increases in white fat depot mass, but also leads to hyperinsulinemia and fat accumulation in brown adipose tissue. Global analysis of the transcriptome of WAT and BAT revealed alterations in gene expression dependent on flattened GC oscillations and point to increased lipid turnover and lipid uptake in both fat depots.
2022-05-13 | GSE202800 | GEO
Project description:Elevated serum concentrations of glucocorticoids (GCs) result in excessive lipid accumulation in white adipose tissue (WAT) as well as dysfunction of thermogenic brown adipose tissue (BAT) – ultimately leading to the development of obesity and metabolic disease. Here, we examined the impact of cold exposure on the adverse metabolic effects of chronic GC exposure on adipose tissue in rodents.
2022-09-04 | GSE212349 | GEO
Project description:The hypothalamic-pituitary-adrenal (HPA) axis forms a complex neuroendocrine system that interacts directly via feedforward and feedback reactions to regulate the body’s response to stress such as starvation. In contrast with the glucocorticoid receptor (GR), ZBTB32 (zinc finger and BTB domain containing 32) is a transcription factor with very poorly described functional relevance in physiology. We investigated the importance of ZBTB32 on the HPA axis functioning and found that it is essential for the production of glucocorticoids (GCs) in response to starvation, because ZBTB32-/- mice fail to increase the GC production during prolonged absence of nutrients. In terms of mechanism, GR-mediated upregulation of adrenal Scarb1 gene expression was absent in ZBTB32-/- mice, implicating defective cholesterol import as the cause of the poor GC synthesis. Lower GC levels in ZBTB32-/- mice are further associated with aberrations in the metabolic adaptation to starvation, which could potentially explain the progressive weight gain of ZBTB32-/- mice. Moreover, this study identifies that ZBTB32 performs a crosstalk with the GR in the metabolic adaptation to starvation via regulation of adrenal GC production.
2021-06-08 | GSE176277 | GEO
Project description:This a model from the article:
Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal
axis model reveals bistability.
Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. Theor Biol Med Model
2007 Feb 14;4:8 17300722
,
Abstract:
BACKGROUND: The body's primary stress management system is the hypothalamic
pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental
challenge to maintain homeostasis in part by controlling the body's cortisol
level. Dysregulation of the HPA axis is implicated in numerous stress-related
diseases. RESULTS: We developed a structured model of the HPA axis that includes
the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of
pituitary GR synthesis. The nonlinear effect arises from the fact that GR
homodimerizes after cortisol activation and induces its own synthesis in the
pituitary. This homodimerization makes possible two stable steady states (low
and high) and one unstable state of cortisol production resulting in bistability
of the HPA axis. In this model, low GR concentration represents the normal
steady state, and high GR concentration represents a dysregulated steady state.
A short stress in the normal steady state produces a small perturbation in the
GR concentration that quickly returns to normal levels. Long, repeated stress
produces persistent and high GR concentration that does not return to baseline
forcing the HPA axis to an alternate steady state. One consequence of increased
steady state GR is reduced steady state cortisol, which has been observed in
some stress related disorders such as Chronic Fatigue Syndrome (CFS).
CONCLUSION: Inclusion of pituitary GR expression resulted in a biologically
plausible model of HPA axis bistability and hypocortisolism. High GR
concentration enhanced cortisol negative feedback on the hypothalamus and forced
the HPA axis into an alternative, low cortisol state. This model can be used to
explore mechanisms underlying disorders of the HPA axis.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230111 | BioModels
Project description:This a model from the article:
Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal
axis model reveals bistability.
Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. Theor Biol Med Model
2007 Feb 14;4:8 17300722
,
Abstract:
BACKGROUND: The body's primary stress management system is the hypothalamic
pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental
challenge to maintain homeostasis in part by controlling the body's cortisol
level. Dysregulation of the HPA axis is implicated in numerous stress-related
diseases. RESULTS: We developed a structured model of the HPA axis that includes
the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of
pituitary GR synthesis. The nonlinear effect arises from the fact that GR
homodimerizes after cortisol activation and induces its own synthesis in the
pituitary. This homodimerization makes possible two stable steady states (low
and high) and one unstable state of cortisol production resulting in bistability
of the HPA axis. In this model, low GR concentration represents the normal
steady state, and high GR concentration represents a dysregulated steady state.
A short stress in the normal steady state produces a small perturbation in the
GR concentration that quickly returns to normal levels. Long, repeated stress
produces persistent and high GR concentration that does not return to baseline
forcing the HPA axis to an alternate steady state. One consequence of increased
steady state GR is reduced steady state cortisol, which has been observed in
some stress related disorders such as Chronic Fatigue Syndrome (CFS).
CONCLUSION: Inclusion of pituitary GR expression resulted in a biologically
plausible model of HPA axis bistability and hypocortisolism. High GR
concentration enhanced cortisol negative feedback on the hypothalamus and forced
the HPA axis into an alternative, low cortisol state. This model can be used to
explore mechanisms underlying disorders of the HPA axis.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230036 | BioModels
Project description:Brown adipose tissue (BAT) evolved in mammals as a natural defence system against hypothermia and obesity. While existence of BAT in adult humans has been recently appreciated, its cellular origin and molecular identity remain elusive due in large to high cellular heterogeneity within adipose tissues. Here we isolated clonal adipocytes from adult human BAT as well as WAT (control) and critically analyzed their transcriptome to identify bona fide BAT markers and its new functions.
2015-01-16 | E-MTAB-2602 | biostudies-arrayexpress
Project description:Background: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. Fsp27 is expressed in both BAT and WAT and promotes lipid storage and the development of obesity and diabetes. In addition, Fsp27-deficient white adipocytes acquired certain BAT-like properties including reduced lipid droplet size and increased mitochondrial activity. Using microarray and semi-quantitative real-time PCR analyses, we systematically analyzed the gene expression profile in Fsp27-deficient WAT and BAT. Results: We observed that BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of Fsp27-/- mice. Expression levels of BAT-selective genes were also dramatically up-regulated in the WAT of leptin and Fsp27 double deficient mice. Furthermore, we observed that expression levels of genes in multiple metabolic pathways including oxidative phosphorylation, the TCA cycle and fatty acid synthesis and oxidation were increased in the Fsp27-/- WAT. In contrast, expression levels for extracellular matrix remodeling, the classic complement pathway and TGF-β signaling"were down-regulated in the WAT of Fsp27-/- mice. Most importantly, regulatory factors that determine BAT identity such as CEBPα/β, PRDM16 and major components in the cAMP pathway were markedly up-regulated in the WAT of Fsp27-/- mice. Interestingly, we observed distinct gene expression profiles in the BAT of Fsp27-/- mice. Conclusion: Our data suggest that Fsp27 acts at upstream to control gene expression of diverse pathways, in particular the expression of regulatory factors that determine the identity of BAT and WAT. Therefore, Fsp27 is an important molecular determinant for the identity of WAT, and loss of Fsp27 leads to the conversion of WAT to a BAT-like tissue. Total RNAs were extracted from individual gonadal WAT of five pairs of 3-month-old wild-type and Fsp27-null male mice. Equal amounts of RNA from five pairs of mice with each genotype were pooled to form RNA pools (total 45 μg). Duplicate experiments were carried out.
2010-07-07 | E-GEOD-22693 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE163242 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162673 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162155 | GEO