Dysregulated hepatic de novo lipogenesis contributes to the pathogenesis of nonalcoholic fatty liver disease in both humans and rodents. Clinical evidence suggests fatty liver to have a positive correlation with serum lead (Pb2+ ) levels. However, an exact mechanism of Pb2+ -induced fatty liver progression is still unknown. Here, we show that exposure to Pb2+ regulates ChREBP-dependent hepatic lipogenesis. Presence of Pb2+ ions within the hepatocytes reduces transcript and protein levels of sorcin, a cytosolic adaptor partner of ChREBP. Adenovirus-mediated overexpression of sorcin in Pb2+ exposed hepatocytes and an in vivo mouse model ameliorates liver steatosis and hepatotoxicity. Hereby, we present Pb2+ exposure to be a lethal disruptor of lipid metabolism in hepatocytes and highlight sorcin as a novel therapeutic target against Pb2+ -induced hepatic dyslipidemia.
Keywords: ChREBP; Pb2+; hepatic de novo lipogenesis; non-alcoholic fatty liver diseases; sorcin.
© 2019 Federation of European Biochemical Societies.