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Int. J. Environ. Res. Public Health 2017, 14(7), 787; https://doi.org/10.3390/ijerph14070787

Airborne PM2.5-Induced Hepatic Insulin Resistance by Nrf2/JNK-Mediated Signaling Pathway

1
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
2
Sino-Danish College, University of Chinese Academy of Sciences, No. 3 Zhongguancun South 1st Alley, Beijing 100190, China
*
Authors to whom correspondence should be addressed.
Received: 8 June 2017 / Revised: 7 July 2017 / Accepted: 10 July 2017 / Published: 14 July 2017
(This article belongs to the Section Environmental Health)
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Abstract

Animal and epidemiological studies have suggested that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is associated with the risk of developing type 2 diabetes. However, the mechanism underlying this risk is poorly understood. In the present study, we investigated the effects of PM2.5 exposure on glucose homeostasis and related signaling pathways in mice. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (Nrf2/) C57BL/6 male mice were exposed to either ambient concentrated PM2.5 or filtered air (FA) for 12 weeks through a whole-body PM exposure system. At the end of the exposure, we assessed liver damage, and performed metabolic studies, gene expressions, as well as molecular signal transductions to determine the signaling pathways involving oxidative responses, insulin signaling, and glucose metabolism. Our results indicated that PM2.5 exposure for 12 weeks caused significant liver damage as evidenced by elevated levels of aminotransferase (AST) and alanine aminotransferase (ALT). Furthermore, PM2.5 exposure induced impaired glucose tolerance and inhibited glycogen synthesis, leading to hepatic insulin resistance indicated by higher glucose levels, higher area under the curve (AUC), and homeostasis model assessment of insulin resistance (HOMA-IR) values. We further found that PM2.5 exposure significantly increased the expressions of Nrf2 and Nrf2-regulated antioxidant genes. Moreover, PM2.5 exposure activated the c-Jun N-terminal kinase (JNK) signaling pathway and increased insulin receptor substrate-1 (IRS-1) phosphorylation at Ser307, but reduced protein kinase B phosphorylation at Ser473. Taken together, our study demonstrated PM2.5 exposure triggered Nrf2-mediated oxidative responses and activated the JNK-mediated inhibitory signaling pathway, resulting in hepatic insulin resistance. View Full-Text
Keywords: PM2.5; liver; insulin resistance; oxidative stress; Nrf2; JNK/IRS-1/AKT PM2.5; liver; insulin resistance; oxidative stress; Nrf2; JNK/IRS-1/AKT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Xu, J.; Zhang, W.; Lu, Z.; Zhang, F.; Ding, W. Airborne PM2.5-Induced Hepatic Insulin Resistance by Nrf2/JNK-Mediated Signaling Pathway. Int. J. Environ. Res. Public Health 2017, 14, 787.

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