Effect of Inhibiting Upstream Aryl Hydrocarbon Receptor Nuclear Translocator on the TCDD-induced Non-alcoholic Fatty Liver Disease

Environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from industrial by-product is a dominant trigger of Non-alcoholic fatty liver disease (NAFLD) that induces an excess triglycerides buildup within the liver. This paper discusses whether knockout of upstream Aryl hydrocarbon receptor nuclear translocator (ARNT) relieves the liver burden in preventing abnormal lipid accumulation after TCDD exposure. This experiment utilizes two models (1) in vivo mice model and (2) in vitro human normal liver cell line model. The ARNT gene is knockout by CRISPR, and the expression of AhR-ARNT complex is detected. Intracellular copper transport assay, mitochondrial OCR analysis, liver function test and histology are then used to observe the ARNT-/- gene regulation and liver cell responses in both models. The most possible result is that ARNT knockout inhibits the TCDD-induced liver toxicity at the initial binding site without affecting the downstream gene regulation; both in vitro and in vivo models present a healthy liver state. The results will contribute crucial information on the TCDD-elicited gene regulation mechanism inside the liver cell, providing detailed environmental toxicant-triggered model studies relate to NAFLD. Prospective studies should focus on investigating the in detail potential side effects of ARNT knockout on the liver and other relative organs.