Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cell Metab. 2011 Mar 2;13(3):249-59. doi: 10.1016/j.cmet.2011.02.005.
Adipocytes store triglyceride during periods of nutritional affluence and release free fatty acids during fasting through coordinated cycles of lipogenesis and lipolysis. While much is known about the acute regulation of these processes during fasting and feeding, less is understood about the transcriptional basis by which adipocytes control lipid handling. Here, we show that interferon regulatory factor 4 (IRF4) is a critical determinant of the transcriptional response to nutrient availability in adipocytes. Fasting induces IRF4 in an insulin- and FoxO1-dependent manner. IRF4 is required for lipolysis, at least in part due to direct effects on the expression of adipocyte triglyceride lipase and hormone-sensitive lipase. Conversely, reduction of IRF4 enhances lipid synthesis. Mice lacking adipocyte IRF4 exhibit increased adiposity and deficient lipolysis. These studies establish a link between IRF4 and the disposition of calories in adipose tissue, with consequences for systemic metabolic homeostasis.
脂肪细胞在营养充足的时期储存甘油三酯，在禁食期间通过脂生成和脂解的协调循环释放游离脂肪酸。虽然人们对禁食和进食期间这些过程的急性调节有了很多了解，但对于脂肪细胞控制脂质处理的转录基础了解较少。在这里，我们表明干扰素调节因子 4 (IRF4) 是脂肪细胞对营养供应的转录反应的关键决定因素。禁食以胰岛素和 FoxO1 依赖的方式诱导 IRF4。IRF4 是脂解所必需的，至少部分原因是直接影响脂肪细胞甘油三酯脂肪酶和激素敏感脂肪酶的表达。相反，降低 IRF4 会增强脂肪合成。缺乏脂肪细胞 IRF4 的小鼠表现出肥胖增加和脂解缺陷。这些研究将 IRF4 与脂肪组织中卡路里的处置联系起来，对全身代谢稳态产生影响。
