Chronic exposure to Pb 2+ perturbs ChREBP transactivation and coerces hepatic dyslipidemia

FEBS Letters

article

P. Vineeth Daniel¹  Mohan Kamthan²  Ruchi Gera³  Surbhi Dogra¹  Krishna Gautam⁴  Debabrata Ghosh²  Prosenjit Mondal¹ 

[1] School of Basic Sciences, Indian Institute of Technology Mandi;Department of Biochemistry, School of Chemical and Life Sciences Jamia Hamdard;Immunotoxicology Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR);Ecotoxicology Division, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR)

关键词: ChREBP;    hepatic de novo lipogenesis;    non-alcoholic fatty liver diseases;    Pb2+;    sorcin;   

DOI  :  10.1002/1873-3468.13538

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ChREBPdependent 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.

【 授权许可】

Unknown