Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2.

Background: Chronic exposure to fine ambient particulate matter (PM) induces insulin resistance. CC-chemokine receptor 2 (CCR2) appears to be essential in diet-induced insulin resistance implicating an important role for systemic cellular inflammation in the process. We have previously suggested that CCR2 is important in PM exposure-mediated inflammation leading to insulin resistance under high fat diet situation. The present study assessed the importance of CCR2 in PM exposure-induced insulin resistance in the context of normal diet.

Methods And Results: C57BL/6 and CCR2 mice were subjected to exposure to concentrated ambient PM or filtered air for 6 months. In C57BL/6 mice, concentrated ambient PM exposure induced whole-body insulin resistance, macrophage infiltration into the adipose tissue, and upregulation of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. While CCR2 deficiency reduced adipose macrophage content in the PM-exposed animals, it did not improve systemic insulin resistance. This lack of improvement in insulin resistance was paralleled by increased hepatic expression of genes in PEPCK and inflammation.

Conclusion: CCR2 deletion failed to attenuate PM exposure-induced insulin resistance in mice fed on normal diet. The present study indicates that PM may dysregulate glucose metabolism directly without exerting proinflammatory effects.