Title: An 'omics approach to unraveling the paradoxical effect of diet on PFOS and PFNA induced NAFLD

Accession Number: GSE138602

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138602

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by array

Organism(s): Mus musculus

Summary: Perfluoroalkyl substances (PFASs) are a family of toxicants universally detected in human serum and known to cause dyslipidemia in animals and humans. Non-alcoholic fatty liver disease (NAFLD) is most prevalent form of liver disease in the United States and has been rising in global prevalence over recent years. This study explored diet-PFAS interactions and their potential role in the increasing global incidence of NAFLD. Male C57BL/6 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) at a low dose of 0.0003 w/w in feed for 12 weeks.Livers were excised for histology and quantification of PFASs and lipids. Proteomics and transcriptomics were utilized to conduct mechanistic pathway exploration. In a high fat diet, PFOS and PFNA protected against the onset of hepatic lipid accumulation and inflammatory progression. Genes and proteins related to lipid metabolism, synthesis, transport, and storage were modulated by PFAS exposure and further impacted by the presence of dietary fat. When combined with a high fat diet, low dose PFOS and PFNA are protective against the onset of NAFLD suggesting that dietary fat impacts the behavior of PFASs in vivo. Furthermore, both dietary fat content and the chemical functional head group exerted significant influence on tissue partitioning and the resulting hepatic biochemical signature. We analyzed a total of 18 samples, using 3 biological replicates per treatment group. Relative gene expression was compared between the low fat diet (LFD) controls, high fat diet (HFD) controls, low fat-PFOS (L-PFOS), low fat-PFNA (L-PFNA), high fat-PFOS (H-PFOS), and high fat-PFNA (H-PFNA) treatment groups.