Chronic exposure to Pb²⁺ perturbs Ch<scp>REBP</scp> transactivation and coerces hepatic dyslipidemia

Abstract

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 (Pb 2+ ) levels. However, an exact mechanism of Pb 2+ ‐induced fatty liver progression is still unknown. Here, we show that exposure to Pb 2+ regulates Ch REBP ‐dependent hepatic lipogenesis. Presence of Pb 2+ ions within the hepatocytes reduces transcript and protein levels of sorcin, a cytosolic adaptor partner of Ch REBP . Adenovirus‐mediated overexpression of sorcin in Pb 2+ exposed hepatocytes and an in vivo mouse model ameliorates liver steatosis and hepatotoxicity. Hereby, we present Pb 2+ exposure to be a lethal disruptor of lipid metabolism in hepatocytes and highlight sorcin as a novel therapeutic target against Pb 2+ ‐induced hepatic dyslipidemia.