Regulation of metabolism by the innate immune system

Key Points Obesity increases production of proinflammatory cytokines that interfere with the insulin signalling pathway In the obese state, chemotactic signals originating from inflamed adipose tissue, liver and muscle lead to monocyte infiltration, polarization of proinflammatory macrophages, tissue inflammation and insulin resistance In adipose tissue in the lean state, group 2 innate lymphoid cells and eosinophils maintain a type 2 cytokine environment by promoting polarization of alternatively activated macrophages Liver Kupffer cells become activated in obesity and secrete chemokines that induce the accumulation of proinflammatory liver macrophages, which contribute to insulin resistance and hepatic steatosis Macrophage infiltration participates in muscle and pancreas inflammation; however, further research is necessary to determine whether such inflammation is causally related to either muscle insulin resistance or β-cell dysfunction Anti-inflammatory treatments have proven less effective at promoting insulin sensitization in humans than in rodents; consequently, demonstrating clear-cut treatment effects for patients remains a future translational challenge