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Epidemiological and experimental studies have indicated that ambient fine particulate matter (PM 2.5) exposure is associated with the occurrence and development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). However, the mechanism is not clear yet, and there are few studies to explore the possible prevention measure. In this study, C57BL/6 and db/db mice were exposed to concentrated PM 2.5 or filtered air using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 12 weeks. From week 11, some of the mice were assigned to receive a subcutaneous injection of AMPK activator (AICAR). Lipid metabolism, glucose tolerance, insulin sensitivity and energy homeostasis were measured. Meanwhile, the respiratory, systemic and visceral fat inflammatory response was detected. The results showed that PM 2.5 exposure induced the impairments of glucose tolerance, insulin resistance, lipid metabolism disorders and disturbances of energy metabolism in both C57BL/6 and db/db mice. These impairments might be consistent with the increased respiratory, circulating and visceral adipose tissue (VAT) inflammatory response, which was characterized by the release of IL-6 and TNF-α in lung, serum and VAT. More importantly, AICAR administration led to the significant enhancement of energy metabolism, elevation of AMPK as well as the decreased IL-6 and TNF-α in VAT of PM 2.5 -exposed mice, which suggesting that AMPK activation might attenuate the inflammatory responses in VAT via the inhibition of MAPKs and NFκB. The study indicated that exposure to ambient PM 2.5 under the concentration which is often seen in some developing countries could induce the occurrence of metabolic disorders in normal healthy mice and exacerbate metabolic disorders in diabetic mice. The adverse impacts of PM 2.5 on insulin sensitivity, energy homeostasis, lipid metabolism and inflammatory response were associated with AMPK inhibition. AMPK activation might inhibit PM 2.5 -induced metabolic disorders via inhibition of inflammatory cytokines release. These findings suggested that AMPK activation is a potential therapy to prevent some of the metabolic disorders attributable to air pollution exposure. • Exposure to ambient PM 2.5 could induce metabolic disorders in normal healthy mice. • Exposure to ambient PM 2.5 could exacerbate metabolic disorders in diabetic mice. • The adverse impacts of PM 2.5 were associated with AMPK inhibition. • AMPK activation might inhibit PM 2.5 -induced metabolic disorders. [ABSTRACT FROM AUTHOR]

Abstract Epidemiological evidences have indicated that fine particulate matter (PM 2.5) is associated with the increased risk of cardiovascular morbidity and mortality. Although several mechanisms linking PM 2.5 and inflammatory responses have been widely implicated, the detailed mechanisms involving the occurrence of inflammation in PM 2.5 -induced adverse effects are lacking. This study aims to investigate whether PM 2.5 exposure-induced cardiovascular injury is associated with NLRP3 inflammasome activation in apolipoprotein E-/- (Apo E-/-) mice. Thirty-two Apo E-/- mice were randomly divided into four groups. The mice were fed with normal chow (NC) or high-fat chow (HFC) for 10 weeks, respectively. From week 11, the mice were exposed to concentrated PM 2.5 (PM) or filter air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. The cardiac function and myocardial injury were evaluated by echocardiography and histopathological examination. Meanwhile, the expression of NLRP3-related signaling pathway in myocardium was detected. Compared with the FA mice, the PM mice showed the underlying cardiac dysfunction and injury in both NC and HFC groups. Mononuclear macrophages (CD11c+) were significant higher in bone marrow of the PM mice than that in the FA mice, whilst CD206+ macrophages were lower. Accordingly, PM 2.5 exposure induced the increase of circulating inflammatory cytokine TNF-α and decrease of anti-inflammatory cytokine IL-10. PM 2.5 exposure was also associated with the activation of NLRP3 inflammasome, which characterized by elevated protein expression of NLRP3, ASC, caspase-1, IL-1β and IL-18 in myocardium. All these results demonstrated PM 2.5 -related cardiac injury is mediated by macrophages polarization and NLRP3 inflammasome activation. Graphical abstract fx1 Highlights • METAS is the first animal exposure system that has been established in China. • We explored the effects of PM 2.5 exposure with NLRP3 inflammasome activation. • M1 macrophages contributed to PM 2.5- induced cardiovascular injury. [ABSTRACT FROM AUTHOR]