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
Low-grade tissue inflammation induced by obesity can result in insulin resistance, which in turn is a key cause of type 2 diabetes mellitus. Cells of the innate immune system produce cytokines and other factors that impair insulin signalling, which contributes to the connection between obesity and the onset of type 2 diabetes mellitus. Here, we review the innate immune cells involved in secreting inflammatory factors in the obese state. In the adipose tissue, these cells include proinflammatory adipose tissue macrophages and natural killer cells. We also discuss the role of innate immune cells, such as anti-inflammatory adipose tissue macrophages, eosinophils, group 2 innate lymphoid cells and invariant natural killer T cells, in maintaining an anti-inflammatory and insulin-sensitive environment in the lean state. In the liver, both Kupffer cells and recruited hepatic macrophages can contribute to decreased hepatic insulin sensitivity. Proinflammatory macrophages might also adversely affect insulin sensitivity in the skeletal muscle and pancreatic β-cell function. Finally, this Review provides an overview of the mechanisms for regulating proinflammatory immune responses that could lead to future therapeutic opportunities to improve insulin sensitivity.
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The authors declare no competing financial interests.
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Lackey, D., Olefsky, J. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol 12, 15–28 (2016). https://doi.org/10.1038/nrendo.2015.189
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