Publication Date:
2019
Description:
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.
Print ISSN:
0014-5793
Electronic ISSN:
1873-3468
Topics:
Biology
,
Chemistry and Pharmacology
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