Wang Kai, Wang Yuan-Yuan, Wu Liang-Liang, Jiang Li-Yan, Hu Yin, Xiao Xin-Hua, Wang Ya-Di
Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Endocrinology. 2022 Jun 1;163(6). doi: 10.1210/endocr/bqac062.
Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to proinflammatory M1 phenotypes on stimulation by microenvironmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization; however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT microenvironment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural, and lymphatic tissues throughout, which together orchestrate the AT microenvironment. Here, we summarize how the aforesaid neighbors of ATMs in the AT microenvironment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.
肥胖最近被定义为一种慢性低度炎症性疾病。肥胖诱导的脂肪组织（AT）炎症是胰岛素抵抗（IR）及相关代谢疾病的重要触发因素。尽管这种炎症的潜在分子基础尚未完全明确，但人们一致认为，AT中募集并被激活的巨噬细胞是AT慢性炎症的最重要元凶。脂肪组织巨噬细胞（ATM）具有高度可塑性，在肥胖AT的微环境信号刺激下，可从抗炎性M2表型极化为促炎性M1表型。人们已做出诸多努力来阐明巨噬细胞极化的分子信号通路；然而，很少有人总结调控和激活巨噬细胞极化的上游驱动因素，尤其是来自AT微环境的调控信息。除脂肪细胞外，AT床还包含各种免疫细胞、干细胞以及贯穿其中的血管、神经和淋巴组织，它们共同协调AT微环境。在此，我们总结了AT微环境中上述与ATM相邻的成分如何向ATM传递信息，从而在肥胖期间调节其表型。破解肥胖环境中ATM的生物学特性和极化机制有望为脂肪炎症及肥胖相关代谢疾病提供精准免疫疗法。
