Zhang Jing, Zhang Lei, Zhang Shu, Yu Qilin, Xiong Fei, Huang Kun, Wang Cong-Yi, Yang Ping
The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education and Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, 1095 Jiefang Ave., Wuhan, 430030, China.
Tongji School of Pharmacy, Huazhong University of Science & Technology, Wuhan 430030, China.
Mol Cell Endocrinol. 2017 Oct 15;454:103-111. doi: 10.1016/j.mce.2017.06.012. Epub 2017 Jun 12.
Obesity has emerged as an imminent global public health concern over the past several decades. It has now become evident that obesity is characterized by the persistent and low-grade inflammation in the adipose tissue, and serves as an independent risk factor for many metabolic disorders such as diabetes and cardiovascular disease. Particularly, adipocytes originated from obese mice and humans likely predominate necrosis upon stressful insults, leading to passive release of cellular contents including the high mobility group box 1 (HMGB1) into the extracellular milieu. Extracellular HMGB1 acts as an innate alarmin to stimulate the activation of resident immune cells in the adipose tissue. Upon activation, those resident immune cells actively secrete additional HMGB1, which in turn activates/recruits additional immune cells, and induces adipocyte death. This review summarizes those novel discoveries in terms of HMGB1 in the initiation and maintenance of chronic inflammatory state in adipose tissue in obesity, and discusses its potential application in clinical settings.
在过去几十年里，肥胖已成为迫在眉睫的全球公共卫生问题。现在已经很明显，肥胖的特征是脂肪组织中持续存在的低度炎症，并且是许多代谢紊乱（如糖尿病和心血管疾病）的独立危险因素。特别是，源自肥胖小鼠和人类的脂肪细胞在应激损伤时可能主要发生坏死，导致包括高迁移率族蛋白B1（HMGB1）在内的细胞内容物被动释放到细胞外环境中。细胞外HMGB1作为一种先天性警报素，刺激脂肪组织中驻留免疫细胞的激活。激活后，这些驻留免疫细胞会主动分泌更多的HMGB1，进而激活/招募更多的免疫细胞，并诱导脂肪细胞死亡。本综述总结了关于HMGB1在肥胖症脂肪组织慢性炎症状态的起始和维持方面的这些新发现，并讨论了其在临床环境中的潜在应用。
