miRNA seq mouse liver HFD, PCB126, Aroclor1260 exposure

Exposure to high fat diet (HFD) and persistent organic pollutants including polychlorinated biphenyls (PCBs) is associated with liver injury in human populations and with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. Exposure of HFD-fed male mice to the non-dioxin-like (NDL) PCB mixture Aroclor1260 or to dioxin-like (DL) PCB126 or to the combination caused steatohepatitis and differentially altered the liver proteome with pathways involving epigenetic regulation of gene expression. Here unbiased RNA sequencing of miRNA (miRNA-seq) and subsequent network analysis to characterize the biological pathways altered by HFD and PCB exposure compared to HFD alone. Distinct miRNA expression patterns reveald a potential role of miRNAs in the pathogenesis of NAFLD. These results demonstrate miRNA and transcriptome pathways in PCB-related hepatic inflammation and fibrosis in a mouse model of NAFLD. Overall design: Male C57Bl/6J mice were fed a high fat diet (HFD, 42% kCal from fat) for 12 weeks and exposed to a single oral gavage of vehicle control (corn oil), Aroclor1260 (20 mg/kg), PCB126 (20 µg/kg), or the combination of the doses of Aroclor1260 + PCB126. miRNA was isolated from five mouse livers/experimental exposure using Qiagen miRNA kits. Libraries were prepared from 1 µg of mouse liver RNA the QIAseq miRNA Library Kit. Two sequencing runs were performed on the Illumina NextSeq 500 using the NextSeq 500/550 High Output Kit v2.5 (75 cycles).