Developmental Exposure to Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) Alters Lipid Metabolism and Lipid Distribution in Zebrafish
Kate Annunziato, Rutgers University
Keith Cooper, Rutgers University
Perfluoroalkylated substances (PFASs) are persistent organic pollutants found in water supplies and human serum samples. While PFOA and PFOS are no longer manufactured, these compounds are resistant to degradation and persistent in the environment. Exposure to PFASs is reported to cause increased lipid accumulation and hepatic steatosis in multiple models. The current study examines the effects of PFOA and PFOS on lipid metabolism in the developing zebrafish. I hypothesize that PFOS and PFOA act through different pathways to alter lipid mobilization and distribution. All exposures of 0.02 - 2 然 PFAS began at 3 hours post fertilization (hpf) and continued to 120 hpf. Gene expression analysis was completed at 120 hpf. Exposure to 0.02- 2 然 PFOS and PFOA caused a significant decrease in expression of proliferator-activated receptor alpha (pparα) and leptin hormone (lepa). PFOA treatment caused a significant reduction in pparγ expression, whereas PFOS treatment caused a significant increase in expression. To examine larvae at 14 days post fertilization (dpf), developmentally exposed larvae were transferred to treatment-free water until 14 dpf at which point whole-mount Oil Red O lipid staining was completed. Exposure to 2 然 PFOA significantly increased hepatic lipid staining and decreased total length. These effects were not observed following 2 然 PFOS treatment. In addition, there were no significant changes in liver area of the larvae. To examine the uptake of lipids from the yolk during early development, microinjections of tagged fatty acids were completed, while the PFAS exposure paradigm remained the same. Yolk sac fluorescence was measured at 24 and 120 hpf. Mean fluorescence was reduced in 2 然 PFOS exposed larvae at 120 hpf, and there was decreased yolk vesicle formation compared to controls. Taken together these studies may partially explain the mechanisms of hepatic steatosis and other alterations in lipid metabolism reported in the zebrafish.