Epidemiological and experimental studies have indicated that ambient fine particulate matter (PM2.5) 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 PM2.5 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 PM2.5 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-alpha 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-alpha in VAT of PM2.5-exposed mice, which suggesting that AMPK activation might attenuate the inflammatory responses in VAT via the inhibition of MAPK5 and NE kappa B. The study indicated that exposure to ambient PM2.5 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 PM2.5 on insulin sensitivity, energy homeostasis, lipid metabolism and inflammatory response were associated with AMPK inhibition. AMPK activation might inhibit PM2.5-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.
[1]Fudan Univ, Dept Environm Hlth, Sch Publ Hlth, Box 249,130 Dongan Rd, Shanghai 200032, Peoples R China;
[2]Shanghai Key Lab Meteorol & Hlth, Shanghai, Peoples R China;
[3]Ohio State Univ, Coll Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA;
[4]Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Cardiol, Shanghai 200127, Peoples R China
(8.0+极速模式)