The effects of perfluorooctanoate on high fat diet induced non-alcoholic fatty liver disease in mice

We reported the hepatic gene expression profiling in mice treated by perfluorooctanoate (PFOA) and high fat diet (HFD). Chronic HFD treatment was associated with gene expression changes in cholesterol biosynthetic process, lipid metabolic process, extracellular matrix, and inflammatory response pathways. Many chemokine related genes including Ccl2, Ccr2, Ccl3l3, Cx3cl1, Cx3cr1, Cxcl14, and toll-like receptor (TLR) related genes including Tlr2, Tlr7, Tlr8, Tlr13 were all significant upregulated comparing vehicle-treated HFD-fed mice to control diet (CD)-fed mice, suggesting their roles in the development of steatohepatitis. PFOA induced gene expression changes in PPAR signaling, fatty acid degradation, biosynthesis of unsaturated fatty acids, and chemical carcinogenesis pathways regardless of diet. However, we showed preexisting fatty liver enhanced the lipid clearance effect of PFOA compared to that in a normal liver. At last, chronic exposure to HFD and PFOA was found to interact on genes related to PPAR signaling, chemical carcinogenesis, and ABC transporter pathways. Two groups of mice were fed with either a control or high-fat diet for 16 weeks to induce normal or steatotic livers, respectively. Subsequently, mice from each diet group were treated with PFOA or vehicle for another 8 weeks. Each mouse was considered a biological replicate. A total of 4 groups with 4 mice in each group were used.