Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice. (28th July 2016)

• Record Type: Journal Article
• Authors: Zhong, Jixin; Allen, Katryn; Rao, Xiaoquan; Ying, Zhekang; Braunstein, Zachary; Kankanala, Saumya R.; Xia, Chang; Wang, Xiaoke; Bramble, Lori A.; Wagner, James G.; Lewandowski, Ryan; Sun, Qinghua; Harkema, Jack R.; Rajagopalan, Sanjay
• Is Part Of: Inhalation toxicology. Volume 28:Number 9(2016)
• Page Start: 383
• Page End: 392
• Publication Date: 2016-07-28
• Subjects: Air pollution -- inflammation -- insulin resistance -- oxidative stress -- ozone exposure; Pulmonary toxicology -- Animal models -- Periodicals; Pulmonary toxicology -- Periodicals; Air -- Pollution -- Health aspects -- Periodicals; 616.200471
• DOI: 10.1080/08958378.2016.1179373
• Languages: English
• ISSNs: 0895-8378

Abstract

Abstract: Background : Inhaled ozone (O3 ) has been demonstrated as a harmful pollutant and associated with chronic inflammatory diseases such as diabetes and vascular disorders. However, the underlying mechanisms by which O3 mediates harmful effects are poorly understood. Objectives : To investigate the effect of O3 exposure on glucose intolerance, immune activation and underlying mechanisms in a genetically susceptible mouse model. Methods : Diabetes-prone KK mice were exposed to filtered air (FA), or O3 (0.5 ppm) for 13 consecutive weekdays (4 h/day). Insulin tolerance test (ITT) was performed following the last exposure. Plasma insulin, adiponectin, and leptin were measured by ELISA. Pathologic changes were examined by H&E and Oil-Red-O staining. Inflammatory responses were detected using flow cytometry and real-time PCR. Results : KK mice exposed to O3 displayed an impaired insulin response. Plasma insulin and leptin levels were reduced in O3 -exposed mice. Three-week exposure to O3 induced lung inflammation and increased monocytes/macrophages in both blood and visceral adipose tissue. Inflammatory monocytes/macrophages increased both systemically and locally. CD4 + T cell activation was also enhanced by the exposure of O3 although the relative percentage of CD4 + T cell decreased in blood and adipose tissue. Multiple inflammatory genes including CXCL-11, IFN-γ, TNFα, IL-12, and iNOS were up-regulated in visceral adipose tissue. Furthermore, the expression of oxidative stress-related genes such as Cox4, Cox5a, Scd1, Nrf1, and Nrf2, increased in visceral adipose tissue of O3 -exposed mice. Conclusions : Repeated O3 inhalation induces oxidative stress, adipose inflammation and insulin resistance.