Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus
复制标题
脂肪组织炎症对2型糖尿病发展的作用
DOI：
10.1002/cphy.c170040
复制
发表时间：
2019-01-01
影响因子：
5.8
通讯作者：
Kratz, Mario
中科院分区：
文献类型：
--
作者：
Burhans, Maggie S.;Hagman, Derek K.;Kratz, Mario
本综述的目的是总结和讨论脂肪组织炎症如何影响胰岛素敏感性和葡萄糖耐量的现有证据。低级别慢性脂肪组织炎症的特征是巨噬细胞和其他免疫细胞群浸润到脂肪组织中，并向更促炎的白细胞亚型转移。脂肪组织中促炎细胞的浸润与关键趋化因子（如C-C基序趋化因子配体2）、促炎因子（包括肿瘤坏死因子a和白细胞介素1 β和6）的产生增加以及关键的胰岛素致敏脂肪因子脂联素的表达减少有关。在啮齿类动物和人类模型中，脂肪组织炎症始终与过量脂肪和胰岛素抵抗有关。在人类中，与皮下脂肪相比，内脏脂肪炎症与胰岛素抵抗的关系更强、更一致。此外，肥胖小鼠模型中减少脂肪组织炎症的基因改变几乎无一例外地与胰岛素敏感性的改善有关。然而，脂肪组织炎症和胰岛素抵抗之间的分离可以在少数肥胖啮齿类动物模型中观察到，也可以在减肥手术或低热量饮食诱导的体重减轻后的人类中观察到，这说明胰岛素抵抗的病因是多因素的。综上所述，脂肪组织炎症是肥胖症中胰岛素抵抗和2型糖尿病发展的关键因素，其他因素可能包括炎症和其他代谢活跃组织中的脂肪积累。(c) 2019年美国生理学会。
The objective of this comprehensive review is to summarize and discuss the available evidence of how adipose tissue inflammation affects insulin sensitivity and glucose tolerance. Low-grade, chronic adipose tissue inflammation is characterized by infiltration of macrophages and other immune cell populations into adipose tissue, and a shift toward more proinflammatory subtypes of leukocytes. The infiltration of proinflammatory cells in adipose tissue is associated with an increased production of key chemokines such as C-C motif chemokine ligand 2, proinflammatory cytokines including tumor necrosis factor a and interleukins 1 beta and 6 as well as reduced expression of the key insulin-sensitizing adipokine, adiponectin. In both rodent models and humans, adipose tissue inflammation is consistently associated with excess fat mass and insulin resistance. In humans, associations with insulin resistance are stronger and more consistent for inflammation in visceral as opposed to subcutaneous fat. Further, genetic alterations in mouse models of obesity that reduce adipose tissue inflammation are-almost without exception-associated with improved insulin sensitivity. However, a dissociation between adipose tissue inflammation and insulin resistance can be observed in very few rodent models of obesity as well as in humans following bariatric surgery-or low-calorie-diet-induced weight loss, illustrating that the etiology of insulin resistance is multifactorial. Taken together, adipose tissue inflammation is a key factor in the development of insulin resistance and type 2 diabetes in obesity, along with other factors that likely include inflammation and fat accumulation in other metabolically active tissues. (c) 2019 American Physiological Society.