PPAR gamma and C/EBP alpha response to acute cold stress in brown adipose tissue

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 tran-scriptional network resulting in the lipid synthesis to oxidation shift during ther-mogenesis is not completely understood. Here, we report the regulation of two master regulators of adipogenesis, peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP alpha), during acute cold stress in BAT. We found PPAR gamma dissociates from DNA in a fifth of its binding sites and these include Cebpa enhancers, leading to decreased C/EBP alpha expression. This dissociation requires PPAR gamma binding to activating ligands and is thus modulated by diet. Meanwhile, PPAR alpha also detaches from DNA, and co-activator PGC1 alpha associates with ERRa as part of a transcriptional network regu-lating lipid metabolism. Subsequent global replacement of C/EBP alpha by C/EBP beta and its associated transcriptional machinery is required for upregulation of structural lipid synthesis despite general upregulation of fatty acid oxidation.