Inflamed fat: what starts the fire?

Abstract

Obesity is associated with increased macrophage infiltration of adipose tissue, and these macrophages may be an important component of the chronic inflammatory response playing a crucial role in the development of insulin resistance. This prompts the question as to how macrophages infiltrate obese adipose tissue. In this issue of the JCI, Weisberg et al. show the importance of C-C motif chemokine receptor 2 (CCR2) in macrophage recruitment to adipose tissue and the development of obesity and its complications.

Figure 1

Macrophage itinerary in adipose tissue infiltration. (A) Macrophage infiltration occurs after initial rolling and attachment of monocytes to activated endothelial cells. These monocytes then extravasate through the endothelial cell layer and differentiate into macrophages. In this issue of the JCI, Weisberg et al. show that CCL2 and its receptor CCR2 play an important role in macrophage chemotaxis (11). Cross-talk among adipocytes, macrophages, and endothelial cells may aggravate the inflammatory state, resulting in increased secretion of proinflammatory cytokines/chemokines, adipokines, and angiogenic factors. These factors could cause local and/or systemic insulin resistance in a paracrine and/or endocrine fashion, respectively, and might also induce local angiogenesis. (B) Adipose tissue (AT) expansion during weight gain leads to recruitment of macrophages through a variety of signals, which may include local hypoxia. These macrophages predominantly localize around dead adipocytes.