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

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. Various ChIPseq of BAT