Sharma Arya M, Staels Bart
Canada Research Chair for Cardiovascular Obesity Research and Management, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2.
J Clin Endocrinol Metab. 2007 Feb;92(2):386-95. doi: 10.1210/jc.2006-1268. Epub 2006 Dec 5.
Adipose tissue is a metabolically dynamic organ, serving as a buffer to control fatty acid flux and a regulator of endocrine function. In obese subjects, and those with type 2 diabetes or the metabolic syndrome, adipose tissue function is altered (i.e. adipocytes display morphological differences alongside aberrant endocrine and metabolic function and low-grade inflammation).
Articles on the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in adipose tissue of healthy individuals and those with obesity, metabolic syndrome, or type 2 diabetes were sourced using MEDLINE (1990-2006).
Articles were assessed to provide a comprehensive overview of how PPARgamma-activating ligands improve adipose tissue function, and how this links to improvements in insulin resistance and the progression to type 2 diabetes and atherosclerosis.
PPARgamma is highly expressed in adipose tissue, where its activation with thiazolidinediones alters fat topography and adipocyte phenotype and up-regulates genes involved in fatty acid metabolism and triglyceride storage. Furthermore, PPARgamma activation is associated with potentially beneficial effects on the expression and secretion of a range of factors, including adiponectin, resistin, IL-6, TNFalpha, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and angiotensinogen, as well as a reduction in plasma nonesterified fatty acid supply. The effects of PPARgamma also extend to macrophages, where they suppress production of inflammatory mediators. As such, PPARgamma activation appears to have a beneficial effect on the relationship between the macrophage and adipocyte that is distorted in obesity. Thus, PPARgamma-activating ligands improve adipose tissue function and may have a role in preventing progression of insulin resistance to diabetes and endothelial dysfunction to atherosclerosis.
脂肪组织是一个代谢活跃的器官，充当控制脂肪酸通量的缓冲器和内分泌功能的调节者。在肥胖个体以及患有2型糖尿病或代谢综合征的个体中，脂肪组织功能发生改变（即脂肪细胞呈现形态差异以及异常的内分泌和代谢功能及低度炎症）。
使用MEDLINE（1990 - 2006年）检索关于过氧化物酶体增殖物激活受体γ（PPARγ）在健康个体以及肥胖、代谢综合征或2型糖尿病患者脂肪组织中的作用的文章。
对文章进行评估以全面概述PPARγ激活配体如何改善脂肪组织功能，以及这如何与胰岛素抵抗的改善以及向2型糖尿病和动脉粥样硬化进展相关联。
PPARγ在脂肪组织中高度表达，噻唑烷二酮类药物对其激活可改变脂肪分布和脂肪细胞表型，并上调参与脂肪酸代谢和甘油三酯储存的基因。此外，PPARγ激活与对一系列因子的表达和分泌具有潜在有益作用相关，这些因子包括脂联素、抵抗素、白细胞介素 - 6、肿瘤坏死因子α、纤溶酶原激活物抑制剂 - 1、单核细胞趋化蛋白 - 1和血管紧张素原，同时还可减少血浆非酯化脂肪酸供应。PPARγ的作用还扩展至巨噬细胞，在其中抑制炎症介质的产生。因此，PPARγ激活似乎对肥胖中扭曲的巨噬细胞与脂肪细胞之间的关系具有有益作用。所以，PPARγ激活配体可改善脂肪组织功能，并且可能在预防胰岛素抵抗进展为糖尿病以及内皮功能障碍进展为动脉粥样硬化方面发挥作用。
