Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2
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RESEARCH
Open Access
Particulate Air pollution mediated effects on insulin resistance in mice are independent of CCR2 Cuiqing Liu1,2*, Xiaohua Xu2, Yuntao Bai2, Jixin Zhong3, Aixia Wang2, Lixian Sun4, Liya Kong1, Zhekang Ying3, Qinghua Sun2,5 and Sanjay Rajagopalan6*
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: Particulate matter, Insulin resistance, CCR2, Normal diet, Inflammation, Gluconeogenesis
Background Accumulating evidence implicates adverse cardiometabolic consequences of fine particulate matter (PM2.5) exposure, including worsening of insulin sensitivity and/or visceral inflammation/adiposity in mice irrespective of diets [1–4]. It is well known that insulin resistance (IR) is often coupled to a cellular inflammatory response in insulin sensitive tissues including liver and adipose tissue, driving the development of abnormalities in glucose and lipoprotein metabolism [5–8]. Monocyte chemoattractant proteins (MCPs) and their receptors play a pivotal role in tissue inflammatory * Correspondence: [email protected]; [email protected] 1 Basic Medical College, Zhejiang Chinese Medical University, 548 Binwen Rd, Building 15#, Room 303, Hangzhou 310053, China 6 Cardiovascular Research Institute, Case Western Reserve School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, USA Full list of author information is available at the end of the article
responses via recruitment of monocytes to sites of inflammation [9]. Recent studies have demonstrated that C-C Motif Chemokine Ligand 2 (CCL2, also known as MCP1) inhibits insulin-stimulated glucose uptake as well as the adipocyte expression of genes implicated in tissue IR and dysregulated met
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