Chronic exposure to Pb2+ perturbs ChREBP transactivation and coerces hepatic dyslipidemia. Issue 21 (27th July 2019)

• Record Type: Journal Article
• Authors: Vineeth Daniel, P.; Kamthan, Mohan; Gera, Ruchi; Dogra, Surbhi; Gautam, Krishna; Ghosh, Debabrata; Mondal, Prosenjit
• Is Part Of: FEBS letters. Volume 593:Issue 21(2019)
• Page Start: 3084
• Page End: 3097
• Publication Date: 2019-07-27
• Subjects: ChREBP -- hepatic de novo lipogenesis -- non‐alcoholic fatty liver diseases -- Pb2+ -- sorcin; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13538
• Languages: English
• ISSNs: 0014-5793

Abstract

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 ChREBP‐dependent hepatic lipogenesis. Presence of Pb 2+ ions within the hepatocytes reduces transcript and protein levels of sorcin, a cytosolic adaptor partner of ChREBP. 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. Abstract :