Tzanavari T, Giannogonas P, Karalis Katia P
Division of Developmental Biology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou, Athens, Greece.
Curr Dir Autoimmun. 2010;11:145-56. doi: 10.1159/000289203. Epub 2010 Feb 18.
Obesity, an epidemic of our times with rates rising to alarming levels, is associated with comorbidities including cardiovascular diseases, arthritis, certain cancers, and degenerative diseases of the brain and other organs. Importantly, obesity is a leading cause of insulin resistance and type 2 diabetes. As emerging evidence has shown over the last decade, inflammation is one of the critical processes associated with the development of insulin resistance, diabetes and related diseases, and obesity is now considered as a state of chronic low-grade inflammation. Adipose tissue, apart from its classical role as an energy storage depot, is also a major endocrine organ secreting many factors, whose local and circulating levels are affected by the degree of adiposity. Obesity leads to infiltration of the expanded adipose tissue by macrophages and increased levels in proinflammatory cytokines. The first indication for increased cytokine release in obesity was provided by the identification of increased expression of TNF-alpha, a proinflammatory cytokine, in the adipose tissue of obese mice in the early 1990s. TNF-alpha is expressed in and secreted by adipose tissue, its levels correlating with the degree of adiposity and the associated insulin resistance. Targeting TNF-alpha and/or its receptors has been suggested as a promising treatment for insulin resistance and type 2 diabetes. This review will summarize the available knowledge on the role of TNF-alpha in obesity and related processes and the potential implications of the above in the development of new therapeutic approaches for obesity and insulin resistance. Recent data from clinical studies will also be described together with late findings on the pathogenesis of obesity and insulin resistance.
肥胖是我们这个时代的一种流行病，其发病率正上升到令人担忧的水平，它与多种合并症相关，包括心血管疾病、关节炎、某些癌症以及大脑和其他器官的退行性疾病。重要的是，肥胖是胰岛素抵抗和2型糖尿病的主要原因。过去十年出现的证据表明，炎症是与胰岛素抵抗、糖尿病及相关疾病发展相关的关键过程之一，肥胖现在被认为是一种慢性低度炎症状态。脂肪组织除了作为能量储存库的经典作用外，还是一个分泌多种因子的主要内分泌器官，其局部和循环水平受肥胖程度影响。肥胖导致巨噬细胞浸润扩张的脂肪组织，并使促炎细胞因子水平升高。20世纪90年代初，在肥胖小鼠的脂肪组织中发现促炎细胞因子肿瘤坏死因子-α（TNF-α）的表达增加，这是肥胖中细胞因子释放增加的首个迹象。TNF-α在脂肪组织中表达并分泌，其水平与肥胖程度及相关的胰岛素抵抗相关。针对TNF-α和/或其受体被认为是治疗胰岛素抵抗和2型糖尿病的一种有前景的方法。本综述将总结关于TNF-α在肥胖及相关过程中的作用的现有知识，以及上述内容对肥胖和胰岛素抵抗新治疗方法开发的潜在影响。还将描述临床研究的最新数据以及关于肥胖和胰岛素抵抗发病机制的最新发现。
