Hepatic ZIP8-mediated selenium transport contributes to normal liver function

ZIP8 is a multi‐functional electroneutral membrane transporter with substrates including both essential and toxic divalent metals (e.g. zinc, manganese, iron and cadmium) and micronutrient selenite. Despite that ZIP8 is found to be associated with metabolic disorders by GWAS, the physiological and pathological roles of ZIP8 remain to be characterized and its connection to any metabolic pathways has not been identified. Our preliminary results demonstrate that moderate or acute decreases in ZIP8 activity resulted in hepatic pathology. Chronic moderate ZIP8 deficiency in transgenic mice led to spontaneous liver neoplastic nodules with increased oxidative stress, inflammation and fibrosis. And acute ZIP8 decrease in mice via adenovirus induced significant hepatomegaly, injury, inflammation and proliferation in liver. In addition, we found that elevation of ZIP8 induced significant glycogen accumulation while downregulation of ZIP8 decreases the glycogen level in primary hepatocytes and liver. Along with these liver pathology, the selenium level and selenoproteins (including GPX1 and GPX2) significantly decreased after ZIP8 deficiency. Thus ZIP8 plays an important role in maintaining normal hepatic function, likely through regulating selenium homeostasis. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .