Background Studies have found that exposure to ambient fine particulate matters (PM2.5) could lead to liver fibrosis and non-alcoholic fatty liver disease. Type 2 diabetes mellitus (T2DM) patients have severe liver damage due to insulin resistance, lipid accumulation, and inflammation in the liver. It is not clear whether ambient PM2.5 exposure would aggravate liver damage in T2DM patients. Currently, there are few studies on its mechanism.
Objective This experiment is designed to explore the role of AMP-activated protein kinase (AMPK) in liver injury of T2DM mice caused by ambient PM2.5.
Methods Thirty-two six-week-old db/db mice were randomly divided into four groups:filtered air (FA) group, filtered air plus 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (FA-AIC) group, concentrated PM2.5 (PM) group, and concentrated PM2.5 plus AICAR (PM-AIC) group. The mice were exposed using Shanghai Meteorological and Environmental Animal Exposure System (ShanghaiMETAS) 10 h per day for 12 weeks. The FA-AIC and PM-AIC groups received daily intraperitoneal injection of AICAR (250 mg/kg) at week 11 for a total of 2 weeks. The pathological changes of liver were determined after hematoxylin-eosin (HE) staining. The mRNA expression levels of AMPK, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were determined by real-time fluorescent quantitative PCR. The protein expression levels of AMPK, P-AMPK, silent mating type information regulation 2 homolog 1 (SIRT1), P38-mitogen-activated protein kinase (MAPK), P-P38-MAPK, protein kinase B (AKT), and P-AKT were detected by Western blot.
Results The scores of the PM group of liver steatosis, ballooning, lobular inflammation, and portal inflammation were 1.50±0.42, 1.10±0.35, 0.80±0.12, and 0.70±0.16, respectively; the scores of the PM-ACI group were 1.40±0.31, 1.20±0.29, 0.70±0.22, and 0.60±0.18, respectively, which were all higher than those of the FA group (P < 0.05); the FA-AIC group showed lower scores of liver ballooning and lobular inflammation than the FA group (P < 0.05); there were no differences in the above four indicators between the PM-AIC and the PM groups (P > 0.05). The expression of AMPK mRNA in liver was inhibited by PM2.5 exposure; however, the expressions of IL-6 and TNF-α mRNA in liver were elevated by PM2.5 exposure. The mRNA expression of AMPK was increased after AICAR injection in both groups treated with concentrated PM2.5 and filtered air (P < 0.05). The protein expressions of SIRT1 and phosphorylation of AMPK and AKT in the mice exposed to concentrated PM2.5 were significantly lower than those in the mice treated with filtered air (P < 0.05). After AICAR injection, the phosphorylation levels of AMPK and AKT in liver of the mice treated with filtered air increased significantly (P < 0.05), but there was no significant difference in the PM-AIC group (P > 0.05).
Conclusion AMPK inhibition is in association with liver injury in type 2 diabetes mellitus model mice aggravated by ambient PM2.5.
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