Abstract
Brown adipose tissue (BAT) has the ability to burn calories as heat. Utilizing BAT thermogenesis is thus an attractive way to combat obesity. However, the transcriptional network resulting in the lipid synthesis to oxidation shift during thermogenesis is not completely understood. Here, we report the regulation of two master regulators of adipogenesis, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), during acute cold stress in BAT. We found PPARγ dissociates from DNA in a fifth of its binding sites and these include Cebpa enhancers, leading to decreased C/EBPα expression. This dissociation requires PPARγ binding to activating ligands and is thus modulated by diet. Meanwhile, PPARα also detaches from DNA, and co-activator PGC1α associates with ERRα as part of a transcriptional network regulating lipid metabolism. Subsequent global replacement of C/EBPα by C/EBPβ and its associated transcriptional machinery is required for upregulation of structural lipid synthesis despite general upregulation of fatty acid oxidation.
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