Liver Inflammation And Glucose Homeostasis Abnormal Induced By Perfluorooctanoic Acid In Mice

[Objective] Perfluorooctanoic acid is a is well stable of physical and chemical properties, man-made and is widely used in industrial production and daily life, as a persistent organic pollutant that can be contact frequently in daily life, many scholars suggested that perfluorooctanoic acid may cause a series of potential health effects. Earlier researchs have suggested that perfluorooctanoic acid may induced lots of kind toxicological effects, for example a damage on the liver, reduce the function of the immune system, cause stunting and damage to the reproductive system and so on, the most obvious effects induced by perfluorooctanoic acid is liver enlargement, the liver as an important metabolism organ, exposed to perfluorooctanoic acid can lead to lipid metabolism disturbance have been proved by many studies, however, studies indicate that the efforts of perfluorooctanoic acid induced glucose homeostasis were still unclear.Therefore, the objective of this study is to explore the effects on glucose homeostasis after treat with perfluorooctanoic acid, and then for further studies on perfluorooctanoic acid toxicological mechanisms.[Methods] In this study 80 male Balb/c mice were divided into two groups, the control group and the perfluorooctanoic acid treated group, every group contain 40 mice, mice were exposed perfluorooctanoic acid with 28 days.During the treatment the body weight were regularly recorded weekly,20 mice were choosed form each group for tolerance test on the day 25, and the rest of mice were treated with oxygen consumption tests. The liver, muscle, fat, blood were collected, and the weight of those tissues were measured for comparison analysis, the blood biochemical indicators and the content of carbohydrate in liver and muscle also be measured, the levels of inflammation and glucose metabolism gene expression in the liver were evaluated by RT-PCR, at last the glucose metabolism proteins expression were identified through Western-blot and other methods.[Results] 1. The body weight was not significantly between PFOA treatment group and the control group, but liver weight was significant increased, subcutaneous fat and epididymal fat showed a downward trend, brown fat tissue was significantly decreased (p<0.01).2. The blood glucose were significantly higher after fasted for 4 hours or 16 hours (p<0.01), tolerance tests showed the mice glucose and pyruvate tolerance increases and insulin sensitivity3. The treatment group oxygen consumption and respiratory quotient were significantly increased (p <0.05), and showed highly significant differences (p<0.01) during the night when animals were busy at their activity.4. Treatment group serum ALT, ALP, ALB, TBA levels were significantly increased (p<0.05), AST levels increased a little, LDH levels decreased significantly (p<0.01); LDL levels increased (p<0.01), HDL, CHO levels decreased markedly (p<0.05), TG level did not change significantly.5. Liver glycogen, lactic acid, glucose were decrease significantly decreases of mice in treatment groups. What's more, the decreased of carbohydrate was more serious after fasted for 16 hours, and carbohydrate in muscle tissue is relatively stable.6. The TNF-?, IL-1?, IL-6, MCP-1 mRNA expression level in liver were significantly increased compared with the control group.7. The protein expression level of phosphorylated AKT (S473) was increased significantly, but the protein level of total AKT was not changed, in addition, the protein expression levels of phosphorylated GS (S641) and total GS were decreased significantly. The mRNA expression level of Glucose-6-phosphatase was increased significantly, but the mRNA expression level of glucokinase was decreased after treated with PFOA.[Conclusion] There was an effect on body function and metabolism after treated with PFOA (1.25mg/kg/d) for 28 days, the weight of liver and oxygen consumption increased significantly, the initial blood glucose were higher compared with control group after fasting, and the levels of hepatitis indicators were increased in serum, the mRNA expression of inflammatory cytokines in was increased in liver, the carbohydrate levels was decreased after treatment. The protein expression levels of phosphorylated AKT was increased, while the levels of glycogen synthase expression was down regulation. All the data suggested that the animals were under a state of inflammation and dysglycemia after treated with PFOA.