Adipose tissue–resident macrophages contribute to local inflammation in the fat during states of obesity and can trigger insulin resistance and glucose intolerance. A study in mice adds new insight to this immunometabolic axis in obesity by showing how these macrophages can worsen inflammation and disease by recruiting additional myeloid cells from the bone marrow to the fat (Cell Metab. 19, 821–835, 2014).

Prabhakara Nagareddy and his colleagues found a local elevation of the alarmins S100A8 and S100A9 in fat tissue of obese mice. These molecules were shown to activate the TLR4-MyD88 pathway in fat-resident macrophages, resulting in inflammasome activation in these cells and production of active interleukin-1β (IL-1β). Upon release of this cytokine into the circulation, IL-1β reached the bone marrow, where it signaled in common myeloid progenitors and granulocyte progenitors to induce their maturation into monocytes and neutrophils and their eventual homing to the fat tissue.

In this way, fat tissue–resident macrophages help recruit new macrophages to the fat, thus exacerbating the inflammation of this tissue during obesity. The results also give further credence to the notion of targeting IL-1β signaling to treat the metabolic complications of type 2 diabetes.