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Yale J Biol Med. 2014 Jun 6;87(2):127-33. eCollection 2014 Jun.

A dangerous duo in adipose tissue: high-mobility group box 1 protein and macrophages.

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Department of Biomedicine, University of Bergen, Bergen, Norway.


High-mobility group box 1 (HMGB1) protein first made headlines 40 years ago as a non-histone nuclear protein that regulates gene expression. Not so long ago, it was also shown that HMGB1 has an additional surprising function. When released into the extracellular milieu, HMGB1 triggers an inflammatory response by serving as an endogenous danger signal. The pro-inflammatory role of HMGB1 is now well-established and has been associated with several diseases, including sepsis, rheumatoid arthritis, and atherosclerosis. Yet very little is known about its role in obesity, wherein adipose tissue is typified by a persistent, smoldering inflammatory response instigated by high macrophage infiltrate that potentiates the risk of obesity-associated comorbidities. This mini-review focuses on the putative causal relationship between HMGB1 and macrophage pro-inflammatory activation in pathologically altered adipose tissue associated with obesity.


adipocyte; adipose tissue; apoptosis; cell death; crown-like structure; damage-associated molecular patterns; danger signals; diabetes mellitus type 2; free fatty acids; high-mobility group box 1 protein; inflammation; insulin resistance; interleukin-6; lipid droplets; lipolysis; macrophage; necrosis; obesity; pattern-recognition receptors; phagocytosis; tumor-necrosis factor-α

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