The effects of photoperiodism and exposure to bisphenol A on hepatic lipid metabolism in female mice / 中国职业医学

ABSTRACT

OBJECTIVE: To analyze the effects and the underlying mechanisms of photoperiodism and exposure to bisphenol A(BPA) on hepatic lipid metabolism in female mice. METHODS: A 2×2 factorial design was used. The photoperiod factor was set to fixed and shifted photoperiod, and the BPA factor was set to BPA exposure(BPA group) and non-exposure(control group). Specific pathogen free female C57 BL/6 J mice were randomly divided into four groups fixed photoperiod control group, shifted photoperiod control group, fixed photoperiod BPA group, and shifted photoperiod BPA group, with eight rats in each group. The fixed photoperiod mice received a 12 ∶12 hours light-dark cycle, and the shifted photoperiod mice experienced reversed light-dark cycle once a week. Mice in BPA group were administered a dose of BPA 50 μg/kg body weigh by gavage, while mice in control group were given a equal volume of corn oil, once per day, five days per week for 12 weeks. The body weight of mice was measured during the experiment. After 12 weeks, all mice in each group were sacrificed. Plasma was collected and the levels of biochemical parameters were measured. Liver tissues were separated for examination of lipid deposition using oil red O and hematoxylin-eosin staining, and plasma triglyceride levels were measured. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA relative expression of genes of fat metabolism in liver tissues. RESULTS: At the end of the experiment, the body weights of mice were higher than that before the experiment(all P<0.05), but there was no statistically significant difference in body weights among the four groups(all P>0.05). The levels of plasma glucose, triglyceride and activity of alanine aminotransferase were higher in shifted photoperiod mice than that in the fixed photoperiod mice(all P<0.05). The plasma aspartate transaminase level was higher in BAP group than that in control group(P<0.01). The area of lipid staining in hepatic tissue was larger in the shifted photoperiod control group, fixed photoperiod BPA group and shifted photoperiod BPA group(all P<0.05), and hepatic lipid droplets aggregation was increased in these three groups compared with the fixed photoperiod control group. The mRNA relative expression of acetyl-coenzyme A carboxylase alpha(Acaca) was higher in the fixed photoperiod BPA and shifted photoperiod control groups(all P<0.05), compared with the fixed photoperiod control group. The relative expression of Acaca mRNA was lower in the shifted photoperiod BPA group than that in the fixed photoperiod BPA group(P<0.05). The mRNA relative expression of sterol regulatory element binding protein(Srebp) 1 and Srebp2 were significantly higher in the BPA group than that in the control group(all P<0.05). CONCLUSION: Both the single shifted photoperiod or BPA exposure can increase hepatic lipid deposition in female mice. The mechanism may be related to up-regulation of the mRNA expression of Acaca, Srebp1 and Srebp2. The shifted photoperiod in combination of BPA exposure has an antagonistic effect on the expression of Acaca mRNA in liver tissues of female mice.