Chronic exposure to Pb²⁺ perturbs ChREBP transactivation and coerces hepatic dyslipidemia.

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: {{ getKeywords(articleDetailText.words) }}