title: Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2.
abstract: 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 PM2.5exposure-mediated inflammation leading to insulin resistance under high fat diet situation. The present study assessed the importance of CCR2 in PM2.5exposure-induced insulin resistance in the context of normal diet.
  
  
  
  C57BL/6 and CCR2-/-mice were subjected to exposure to concentrated ambient PM2.5or filtered air for 6 months. In C57BL/6 mice, concentrated ambient PM2.5exposure 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.
  
  
  
  CCR2 deletion failed to attenuate PM2.5exposure-induced insulin resistance in mice fed on normal diet. The present study indicates that PM2.5may dysregulate glucose metabolism directly without exerting proinflammatory effects.
authors.affiliation: Basic Medical College, Zhejiang Chinese Medical University, 548 Binwen Rd, Building 15#, Room 303, Hangzhou, 310053, China. liucuiqing@zcmu.edu.cn.|Wexner Medical Center, The Ohio State University, Columbus, OH, USA. liucuiqing@zcmu.edu.cn.
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.affiliation: Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Jixin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.affiliation: Division of Cardiovascular Medicine, The Affiliated Hospital of Chengde Medical College, Chengde, China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Sun
authors.affiliation: Basic Medical College, Zhejiang Chinese Medical University, 548 Binwen Rd, Building 15#, Room 303, Hangzhou, 310053, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Kong
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Zhekang
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Wexner Medical Center, The Ohio State University, Columbus, OH, USA.|College of Public Health, Division of Environmental Health Sciences, The Ohio State University, Columbus, OH, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Cardiovascular Research Institute, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH, 44106, USA. sanjay.rajagopalan@case.edu.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D004032:Diet; D005947:Glucose / Q000378:metabolism; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D054390:Receptors, CCR2 / Q000235:genetics*
chemical_list: D000393:Air Pollutants; C515335:Ccr2 protein, mouse; D007328:Insulin; D052638:Particulate Matter; D054390:Receptors, CCR2; D005947:Glucose
keywords: CCR2; Gluconeogenesis; Inflammation; Insulin resistance; Normal diet; Particulate matter