Zeyda Maximilian, Stulnig Thomas M
Department of Internal Medicine III, Clin. Div. Endocrinology and Metabolism, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Immunol Lett. 2007 Oct 15;112(2):61-7. doi: 10.1016/j.imlet.2007.07.003. Epub 2007 Jul 31.
It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of insulin resistance and type 2 diabetes mellitus. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with production of inflammatory cytokines. Adipose tissue macrophages (ATMs) are suspected to be the major source of inflammatory mediators such as TNF-alpha and IL-6 that interfere with adipocyte function by inhibiting insulin action. However, ATMs phenotypically resemble alternatively activated (M2) macrophages and are capable of anti-inflammatory mediator production challenging the concept that ATMs are simply the "bad guys" in obese adipose tissue. Triggers promoting ATM recruitment, ATM functions and dysfunctions, and stimuli and molecular mechanisms that drive them into becoming detrimental to their environment are subject to current research. Strategies to interfere with ATM recruitment and adverse activation could give rise to novel options for treatment and prevention of insulin resistance and type 2 diabetes mellitus.
目前已广泛接受的观点是,与肥胖相关的低度慢性炎症会导致胰岛素抵抗和2型糖尿病的发生。肥胖相关炎症的特征是脂肪组织中巨噬细胞数量增加以及炎症细胞因子的产生。脂肪组织巨噬细胞(ATM)被怀疑是炎症介质(如肿瘤坏死因子-α和白细胞介素-6)的主要来源,这些炎症介质通过抑制胰岛素作用来干扰脂肪细胞功能。然而,ATM在表型上类似于交替激活的(M2)巨噬细胞,并且能够产生抗炎介质,这对ATM仅仅是肥胖脂肪组织中的“坏人”这一概念提出了挑战。促进ATM募集的触发因素、ATM的功能和功能障碍,以及促使它们对周围环境产生有害影响的刺激因素和分子机制,都是当前研究的主题。干扰ATM募集和不良激活的策略可能会为胰岛素抵抗和2型糖尿病的治疗和预防带来新的选择。