Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation

Obesity-associated adipose tissue inflammation contributes to the development of type 2 diabetes. Chronic activation of IL-1β system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and activation in the tissue has remained unexplored. Here we demonstrate that IL-1β transcript was enriched in neutrophils of white adipose tissue (WAT), and the expression of IL-1β was up-regulated by a high-fat diet in the WAT but not in other tissues, including bone marrow, peripheral blood, and spleen. The co-culture of neutrophils with 3T3-L1 adipocytes indicate that contact interaction with adipocytes is critical for the expression of IL-1β via NF-κB activation in adipose tissue neutrophils. Lipolysis of adipocytes accumulated neutrophils prior to macrophages in the WAT, and produced high levels of IL-1β via an ASC-caspase-1-mediated inflammasome pathway. Leukotriene B4 production in the WAT also contributed to neutrophil accumulation. Furthermore, neutrophils and IL-1β contributed to the expression of chemotactic molecules involved in high-fat diet-induced macrophage infiltration into the WAT. We have identified previously unappreciated roles for neutrophils in the development of adipose tissue inflammation: robust IL-1β production and infiltration of macrophages to initiate chronic inflammation.