Regulation of Nutrient Homeostasis by IRF4

 描述(由申请人提供)：肥胖症和2型糖尿病的有效治疗目前是有限的。一种很有希望的方法是对脂肪细胞进行“重新编程”，以促进卡路里消耗和增强葡萄糖动态平衡。然而，脂肪细胞生理的调节需要我们了解这些细胞调节基因表达的途径。我们已经确定了一种未知的转录因子IRF4，它是脂肪生成、脂肪分解、脂肪生成和产热的关键调节因子。 脂肪细胞。有趣的是，IRF4在免疫细胞中得到了很好的研究，在免疫细胞中，它引导巨噬细胞极化和T细胞分化。在这里，我们将描述在棕色和白色脂肪细胞中调节IRF4表达的途径，并确定该因子在脂肪中的靶基因。此外，我们还将研究在脂肪细胞中调节IRF4活性的转录后机制。这些研究将涉及体内和体外的一些有偏见和不偏不倚的方法。如果成功，这些研究将更好地确定IRF4在脂肪细胞中的生物学作用。IRF4位于脂肪组织中新陈代谢和炎症的交叉点，因此是一个潜在的治疗干预的完美位置。

 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.