Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
Immunology. 2018 Dec;155(4):407-417. doi: 10.1111/imm.13002. Epub 2018 Oct 19.
The expansion of adipose tissue (AT) in obesity is accompanied by the accumulation of immune cells that contribute to a state of low-grade, chronic inflammation and dysregulated metabolism. Adipose tissue macrophages (ATMs) represent the most abundant class of leukocytes in AT and are involved in the regulation of several regulatory physiological processes, such as tissue remodeling and insulin sensitivity. With progressive obesity, ATMs are key mediators of meta-inflammation, insulin resistance and impairment of adipocyte function. While macrophage recruitment from blood monocytes is a critical component of the generation of AT inflammation, new studies have revealed a role for ATM proliferation in the early stages of obesity and in sustaining AT inflammation. In addition, studies have revealed a more complex range of macrophage activation states than the previous M1/M2 model, and the existence of different macrophage profiles between human and animal models. This review will summarize the current understanding of the regulatory mechanisms of ATM function in relation to obesity, type 2 diabetes, depot of origin, and to other leukocytes such as AT dendritic cells, with hopes of emphasizing the regulatory nodes that can potentially be targeted to prevent and treat obesity-related metabolic disorders.
肥胖症患者的脂肪组织（AT）扩张伴随着免疫细胞的积累，这些免疫细胞导致低度、慢性炎症和代谢失调。脂肪组织巨噬细胞（ATMs）是 AT 中最丰富的白细胞类群，参与调节组织重塑和胰岛素敏感性等多种调节生理过程。随着肥胖的进展，ATMs 是代谢炎症、胰岛素抵抗和脂肪细胞功能障碍的关键介质。虽然血液单核细胞向巨噬细胞的募集是 AT 炎症发生的关键组成部分，但新的研究揭示了 ATMs 增殖在肥胖早期和维持 AT 炎症中的作用。此外，研究还揭示了比以前的 M1/M2 模型更复杂的巨噬细胞激活状态范围，以及人类和动物模型之间存在不同的巨噬细胞表型。这篇综述将总结目前对与肥胖症、2 型糖尿病、脂肪组织来源以及与脂肪组织树突状细胞等其他白细胞相关的 ATMs 功能的调节机制的理解，以期强调潜在的调控节点，以预防和治疗肥胖相关的代谢紊乱。
