Discovery of the adipose tissue as a major source of signaling molecules almost three decades ago set a novel physiological paradigm that paved the way for the identification of metabolic organs as endocrine organs. Adipocytes, the main adipose tissue cell type, do not only represent the principal site of energy storage in form of triglycerides, but also produce a variety of molecules for short and long distance intercellular communication, named adipokines, which coordinate systemic responses. Although the best known adipokines identified and characterized hitherto are leptin and adiponectin, novel adipokines are continuously being described, what have significantly helped to elucidate the role of adipocyte biology in obesity and associated comorbidities. One of these novel adipokines is high-mobility group box 1 (HMGB1), a ubiquitous nuclear protein that has been recently reported to be dysregulated in obese dysfunctional adipocytes. Although the classical function of HMGB1 is related to inflammation and immunity, acting as an alarmin, novel advances evidence an active implication of HMGB1 in tissue remodeling and fibrosis. This review summarizes the current evidence on the mechanisms controlling HMGB1 release, as well as its role as a regulator of adipocyte function and extracellular matrix remodeling, with special emphasis on the potential of this novel adipokine as a target in the obesity treatment.

大约 30 年前，脂肪组织作为信号分子的主要来源的发现确立了一种新的生理范式，为将代谢器官识别为内分泌器官铺平了道路。脂肪细胞是主要的脂肪组织细胞类型，不仅以甘油三酯的形式代表能量储存的主要部位，而且还产生多种用于短距离和长距离细胞间通讯的分子，称为脂肪因子，它们协调全身反应。尽管迄今为止鉴定和表征的最著名的脂肪因子是瘦素和脂联素，但仍在不断描述新的脂肪因子，这极大地有助于阐明脂肪细胞生物学在肥胖和相关合并症中的作用。其中一种新型脂肪因子是高迁移率组框 1 (HMGB1)，一种普遍存在的核蛋白，最近据报道它在肥胖的功能失调的脂肪细胞中失调。尽管 HMGB1 的经典功能与炎症和免疫有关，充当警报素，但新的进展证明 HMGB1 在组织重塑和纤维化中具有积极意义。本综述总结了目前关于控制 HMGB1 释放的机制的证据，以及它作为脂肪细胞功能和细胞外基质重塑的调节剂的作用，特别强调了这种新型脂肪因子作为肥胖治疗靶点的潜力。新的进展证明 HMGB1 在组织重塑和纤维化中具有积极意义。本综述总结了目前关于控制 HMGB1 释放的机制的证据，以及它作为脂肪细胞功能和细胞外基质重塑的调节剂的作用，特别强调了这种新型脂肪因子作为肥胖治疗靶点的潜力。新的进展证明 HMGB1 在组织重塑和纤维化中具有积极意义。本综述总结了目前关于控制 HMGB1 释放的机制的证据，以及它作为脂肪细胞功能和细胞外基质重塑的调节剂的作用，特别强调了这种新型脂肪因子作为肥胖治疗靶点的潜力。