Anghel Silvia I, Wahli Walter
Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne CH-1015, Switzerland.
Cell Res. 2007 Jun;17(6):486-511. doi: 10.1038/cr.2007.48.
Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARgamma agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARgamma in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARgamma modulators.
脂肪组织并非仅仅是一个只负责储存脂肪的惰性细胞团，而是一个由具有高度专业化和复杂功能的细胞成分组成的复杂集合体。除了管理身体最重要的能量储备外，它还分泌大量被称为脂肪因子的可溶性蛋白质，这些蛋白质对全身的稳态具有有益或有害的影响。这些脂肪因子的表达是对从许多器官接收到的各种信号的综合反应，这在很大程度上取决于脂肪组织的完整性和生理状态。脂肪中基因表达的主要调节因子之一是转录因子过氧化物酶体增殖物激活受体γ（PPARγ），它是一种依赖脂肪酸和类花生酸的核受体，在脂肪组织的发育和维持中起关键作用。此外，合成的PPARγ激动剂是用于治疗2型糖尿病的治疗药物。本综述讨论了关于脂肪生理学与代谢疾病之间联系的最新知识，以及PPARγ通过调节脂质和葡萄糖代谢在这种相互作用中的作用。最后，我们评估了用尚未确定的高度选择性PPARγ调节剂靶向这种核受体的假定益处。
