Long-read isoform sequencing reveals Aroclor1260-induced isoform expression in mouse liver

Long-term exposure to polychlorinated biphenyls (PCBs) including the mixture of PCBs in Aroclor1260 (Ar1260) results in metabolic dysfunction-associated steatotic liver disease (MASLD) in mice and humans. Previously, we reported that chronic (34 wks.) exposure of normal low fat diet (LFD)-fed male mice to Ar1260 resulted in twelve hepatic RNA modifications. We confirmed the downregulation NRF2 (Nfe2l2) network pathway associated with human liver diseases. Proteomic analysis of these same liver samples identified Ar1260 exposure-associated changes in protein abundance including altered selenoproteins: GPX4 and SELENBP2 were increased and SELENOS and SELENOF were reduced. Alternative splicing (AS) has been implicated in MASLD. Here we used long-read isoform sequencing (IsoSeq) to and differential transcript usage (DTU) to specific DTU gene differences depending on the severity of liver injury with Ar1260.