Regulation of Nutrient Homeostasis by IRF4

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 DESCRIPTION (provided by applicant): Effective therapeutic management of obesity and Type 2 diabetes is currently limited. One promising approach involves the 'reprogramming' of adipocytes in ways that promote calorie expenditure and enhanced glucose homeostasis. Modulation of adipocyte physiology, however, requires that we understand the pathways by which these cells regulate gene expression. We have identified an unsuspected transcription factor, IRF4, as a critical regulator of adipogenesis, lipolysis, lipogenesis, and thermogenesis in adipocytes. Interestingly, IRF4 is well-studied in immune cells, where it directs macrophage polarization and T cell differentiation. Here we will characterize the pathways that regulate IRF4 expression in brown and white adipocytes, and we will identify the target genes of this factor in fat. Furthermore, we will also study the post- transcriptional mechanisms by which IRF4 activity is regulated in adipocytes. These studies will involve a number of biased and unbiased approaches in vivo and in vitro. If successful, these studies will better define the biological actions of IRF4 in adipocytes. IRF4 sits at the intersection of metabolism and inflammation in adipose tissue and is thus perfectly positioned as a site of potential therapeutic intervention.