HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity

- Obesity is characterized by a chronic, low-grade inflammation.
- Both necrotic adipocytes and activated immune cells account for the increased HMGB1 level in obese subjects.
- HMGB1 initiates and maintains chronic inflammatory state in adipose tissue through RAGE and TLRs signaling pathways.
- HMGB1 could be a biomarker for early diagnosis of obesity and therapeutic target for prevention and intervention of obesity-induced inflammation.

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.