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Chronic exposure to Pb 2+ perturbs Ch REBP transactivation and coerces hepatic dyslipidemia
Author(s) -
Vineeth Daniel P.,
Kamthan Mohan,
Gera Ruchi,
Dogra Surbhi,
Gautam Krishna,
Ghosh Debabrata,
Mondal Prosenjit
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13538
Subject(s) - lipogenesis , steatosis , nonalcoholic fatty liver disease , dyslipidemia , fatty liver , transactivation , chemistry , in vivo , endocrinology , medicine , lipid metabolism , biology , biochemistry , diabetes mellitus , transcription factor , gene , disease , microbiology and biotechnology
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.