Open AccessMacrophage-Mediated Effects of Airborne Fine Particulate Matter (PM2.5) on Hepatocyte Insulin Resistance in Vitro
Author(s) -
Ran Li,
Xinghua Qiu,
Fang Xu,
Yan Lin,
Yuguang Fang,
Tong Zhu
Publication year - 2016
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.6b00135
Subject(s) - insulin resistance , insulin receptor , insulin , insulin receptor substrate , protein kinase b , hepatocyte , medicine , endocrinology , tumor necrosis factor alpha , chemistry , phosphorylation , biology , in vitro , microbiology and biotechnology , biochemistry
Fine particulate matter (PM 2.5 ) pollution poses significant health risks worldwide, including metabolic syndrome-related diseases with the characteristic feature of insulin resistance. However, the mechanism and influencing factors of this effect are poorly understood. In this serial in vitro study, we aimed at testing the hypothesis that macrophage-mediated effects of PM 2.5 on hepatic insulin resistance depend on its chemical composition. Mouse macrophages were exposed to PM 2.5 that had been collected during summer or winter in Beijing, which represented different compositions of PM 2.5 . Thereafter, hepatocytes were treated with macrophage-conditioned medium (CM). PM 2.5 induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 expression and secretion in macrophages, particularly after winter PM 2.5 exposure. Correspondingly, winter CM weakened hepatocellular insulin-stimulated glucose consumption. Further investigation revealed that the normal insulin pathway was suppressed in winter CM-treated hepatocytes, with increased phosphorylation of insulin receptor substrate 1 at serine residue 307 (Ser307) and decreased phosphorylation of protein kinase B (PKB/AKT) and forkhead box transcription factor O1 (FoxO1). Moreover, c-Jun N-terminal kinase, a key moderator of the sensitivity response to insulin stimulation, was activated in hepatocytes treated with winter CM. Although further studies are warranted, this preliminary study suggested an association between PM composition and insulin resistance, thus contributing to our understanding of the systemic toxicity of PM 2.5 .