Role of interleukins in obesity: implications for metabolic disease

• The NLRP3 inflammasome is activated in immune cells by islet amyloid polypeptide to increase β cell death.
• The NLRP3 inflammasome can also induce insulin resistance by contributing to hepatosteatosis and adipocyte differentiation.
• The NLRP3 inflammasome may be a therapeutic target to treat type 2 diabetes mellitus.

It has been two decades since the discovery that pro-inflammatory cytokines are expressed in obesity. This initial work was the catalyst for the now-accepted paradigm that nutrient overload promotes inflammation and links the metabolic and immune systems, where inflammation may be pathological. However, inflammation is an adaptive and, importantly, an energy-consuming process. Indeed, the rapid mobilization of stored energy reserves by cytokines such as the interleukins, is critical to mounting any successful inflammatory response. Thus, the role of the interleukins in metabolism and energy homeostasis is more complex than first thought and recent evidence is mounting that, for several interleukins, although excess production is negative, blockade or insufficiency is equally undesirable.