Particulate Air Pollution Mediated Effects on Insulin Resistance in Mice Are Independent of CCR2

Part Fibre Toxicol. 2017 Mar 3;14(1):6. doi: 10.1186/s12989-017-0187-3.

Abstract

Background: Chronic exposure to fine ambient particulate matter (PM2.5) 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 PM2.5 exposure-mediated inflammation leading to insulin resistance under high fat diet situation. The present study assessed the importance of CCR2 in PM2.5 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 PM2.5 or filtered air for 6 months. In C57BL/6 mice, concentrated ambient PM2.5 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 PM2.5-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 PM2.5 exposure-induced insulin resistance in mice fed on normal diet. The present study indicates that PM2.5 may dysregulate glucose metabolism directly without exerting proinflammatory effects.

Keywords: CCR2; Gluconeogenesis; Inflammation; Insulin resistance; Normal diet; Particulate matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / immunology
  • Air Pollutants / toxicity*
  • Animals
  • Diet
  • Glucose / metabolism
  • Inflammation
  • Insulin / metabolism
  • Insulin Resistance*
  • Liver / drug effects
  • Liver / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Particle Size
  • Particulate Matter / toxicity*
  • Receptors, CCR2 / genetics*

Substances

  • Air Pollutants
  • Ccr2 protein, mouse
  • Insulin
  • Particulate Matter
  • Receptors, CCR2
  • Glucose