An ‘Omics Approach to Diet & Structure Impact on Perfluoroalkyl Substance Induced Liver Disease
Perfluoroalkyl substances (PFASs), a family of environmental toxicants, are ubiquitous in the environment and the human population. PFASs are known to augment lipid accumulation and steatosis in the liver. However, there is a lack of knowledge concerning the long-term effects of environmentally relevant doses to common PFASs, in combination with common dietary risk factors, and their potential role in the increasing incidence of NAFLD in the global population. In manuscript 1, male C57BL6 mice were fed with either a low fat diet (10% kcal from fat) or a moderately high fat diet (45% kcal from fat) with or without perfluorooctanesulfonic acid (PFOS) or perfluorononanoic acid (PFNA) 0.0003% w/w in feed for 12 weeks. Proteomics and transcriptomics were utilized to explore the mechanistic pathways driving the liver pathology. In manuscript 2, male C57BL6 mice were fed with either a low-fat diet (11% kcal from fat) or a high fat (58% kcal from fat) high carbohydrate (42g/L) diet with or without PFOS or perfluorohexanesulfonic acid (PFHxS), in feed (0.0003% w/w) for 29 weeks. Sera lipidomics, as well as hepatic proteomics, gene expression, and pathology were used to assess diet-PFAS interactions. In manuscript 1, PFASs were protective against the onset of fatty liver only in combination with a moderately high fat diet. Yet in manuscript 2, PFASs worsened macrovesicular steatosis only in the presence of a high fat high carbohydrate diet. Both studies revealed that diet composition as well as slight alterations in PFAS structure exert significant influence on PFAS related tissue partitioning, liver pathology, and the resulting hepatic biochemical signature.
"An ‘Omics Approach to Diet & Structure Impact on Perfluoroalkyl Substance Induced Liver Disease"
Dissertations and Master's Theses (Campus Access).