Effects Of Bisphenol A Exposure On Lipid Metabolism In Male Zebrafish(Danio Rerio)

Bisphenol A (BPA) is an environmental hormone pollutant which is widely distributed in aquatic environment. The effect on lipid metabolism in mammals has been well studied, but not in fish. Lipid metabolism in fish is related to food safety, fish health and economic benefits. The current research on environmental factors which affect fish lipid metabolism is not sufficient.In order to learn the effect of BPA on fish lipid metabolism, we used zebrafish (Danio rerio) as the test subject. To minimize the impact of gender and age, we used adult male zebrafish as the experimental model. The study is helpful to understand the effects of environmental contaminant on fish lipid metabolism. In addition, it is the first study to investigate the systemic lipid metabolism of male zebrafish exposed to BPA.The research was mainly divided into three parts:1. First of all, zebrafish was exposed in four concentrations (50μg/L、200μg/L 1 000μg/L、2000μg/L) of BPA for 5 weeks. Then we detected the lipid content of liver and muscle. Moreover, we selected the fish from two BPA concentration (200μg/L、 2000μg/L) groups, and the fish liver was used for transcriptomic analysis with Illumina Hisseq2000 platform. The results showed that BPA induced lipid accumulation in male zebrafish, but no dose-response relationship was found. The transcriptomic data proved that both concentrations of BPA led to the increase of pancreatic lipase secretion in zebrafish. This suggests that BPA can promote the digestion and absorption of lipid, and this could be an important reason for the high fat deposit in the zebrafish exposed to BPA.2. To further learn the effect of BPA on fish lipid metabolism, zebrafish was exposed to two concentrations of BPA (200μg/L、2000μg/L) for 5 weeks, then we detected the lipid content and used QRT-PCR to test expression patterns of mRNA related to lipid metabolism. The results showed that lipid content was similar to that in the previous study. The genes related to lipid metabolism in two concentrations of BPA were similar, such as FAS, DGATlb, DGAT2 were significantly increased. The expression of VTG was increased in both groups, and significantly in high concentrations group.3. Due to that BPA can induce pancreatic lipase secretion, and promote the absorption of external fat in zebrafish under normal fat diet, we would like to know the effects of BPA exposure on the lipid metabolism in zebrafish fed with the diets containing different lipid content and the coordination effect of BPA and dietary fat. The zebrafish were exposed to 200ug/L BPA for 5 weeks, and fed with three different diets containing 1.17,6.98,13.11% lipid content, respectively, to explore whether BPA has similar influence on lipid metabolism under different dietary fat background in zebrafish. Then we used molecular, biochemical and histological techniques to test the effect on zebrafish lipid metabolism. The results showed that BPA can cause lipid accumulation in zebrafish liver in three different dietary groups. The low fat diet caused the visceral lipid accumulation, and normal fat diet caused the muscle lipid accumulation. The histology results showed fat cavitation in liver by BPA exposed under different fat diet in zebrafish. The FAS, DGAT2 were significantly increased in normal and high fat diet, but the FAS was significantly decrease in low fat diet group.Conclusion:The study first demonstrated that BPA could induce pancreatic lipase secretion, which could promote the absorption of external fat in zebrafish. In addition, BPA could also cause higher expression of FAS and DGAT, which could promote the synthesis of endogenous lipid. These may be the basic metabolism mechanism of BPA caused disturbance of lipid metabolism and lipid accumulation in male zebrafish. Although our present study has been confirmed that BPA can lead to zebrafish lipid accumulation, the different fat diets and different concentrations of BPA may have different mechanisms to induce fat accumulation and it needs to be studied further.