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PPARg and C/EBPa response to acute cold stress in brown adipose tissue [RNA-seq]

ABSTRACT: Brown adipose tissue (BAT) has the ability to burn calories as heat. BAT thermogenesis is an attractive way to combat obesity pandemic. However, the transcriptional network resulting in lipid synthesis to oxidation shift during thermogenesis is not completely understood. Here, we report the regulation of two master regulators of adipogenesis, PPARγ and C/EBPα, during acute cold stress in BAT. We found PPARγ dissociated from DNA in a third of its binding sites and these included cebpa enhancers leading to decreased C/EBPα. This dissociation required PPARγ binding to activating ligands, thus modulated by diet. Meanwhile PPARα also detached from DNA, and co-activator PGC1α associated with ERR1 as part of transcriptional network regulating lipid metabolism. Subsequent global replacement of C/EBPα by C/EBPβ and its associated transcriptional machinery was required for upregulation of structural lipid synthesis despite general upregulation of fatty acid oxidation.

ORGANISM(S): Mus musculus

PROVIDER: GSE213599 | GEO | 2023/01/11

REPOSITORIES: GEO

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PPARg and C/EBPa response to acute cold stress in brown adipose tissue

Project description:Brown adipose tissue (BAT) has the ability to burn calories as heat. BAT thermogenesis is an attractive way to combat obesity pandemic. However, the transcriptional network resulting in lipid synthesis to oxidation shift during thermogenesis is not completely understood. Here, we report the regulation of two master regulators of adipogenesis, PPARγ and C/EBPα, during acute cold stress in BAT. We found PPARγ dissociated from DNA in a third of its binding sites and these included cebpa enhancers leading to decreased C/EBPα. This dissociation required PPARγ binding to activating ligands, thus modulated by diet. Meanwhile PPARα also detached from DNA, and co-activator PGC1α associated with ERR1 as part of transcriptional network regulating lipid metabolism. Subsequent global replacement of C/EBPα by C/EBPβ and its associated transcriptional machinery was required for upregulation of structural lipid synthesis despite general upregulation of fatty acid oxidation.

2023-05-17 | GSE218516 | GEO

PPARg and C/EBPa response to acute cold stress in brown adipose tissue [ChIP-Seq]

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Brown adipose TRX2 deficiency activates mtDNA-NLRP3 to impair thermogenesis and protect against diet-induced insulin resistance

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Project description:Here we report, for the first time, the acute effects of the synthetic PPARγ agonist rosiglitazone on the transcriptional network of PPARγ in adipocytes. Treatment with Rosiglitazone for 1 hour leads to acute transcriptional activation as well as repression of a number of genes as determined by genome-wide RNA polymerase II occupancy. Unlike what has been shown for many other nuclear receptors, agonist treatment does not lead to major changes in the occurrence of PPARγ binding sites. However, rosiglitazone promotes PPARγ occupancy at many preexisting sites, and this is paralleled by increased occupancy of the mediator subunit MED1. The increase in PPARγ and MED1 binding is correlated with an increase in transcription of nearby genes indicating that rosiglitazone, in addition to activating the receptor, also promotes its association with DNA, and that this is causally linked to recruitment of mediator and activation of genes. Notably, both Rosiglitazone-activated and -repressed genes are induced during adipogenesis. However, Rosiglitazone-activated genes are markedly more associated with PPARγ than repressed genes and are highly dependent on PPARγ for expression in adipocytes. By contrast, repressed genes are associated with the other key adipocyte transcription factor CCAAT-Enhancer binding protein (C/EBPα), and their expression is more dependent on C/EBPα. This suggests that the relative occupancies of PPARγ and C/EBPα are critical for whether genes will be induced or repressed by PPARγ agonist. Examination of binding of PPARγ, C/EBPα, RNAPII, CBP and MED1 in mature 3T3-L1 adipocytes treated with 1 μM Rosiglitazone and/or 0.1% DMSO for 1 hour.

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