Investigating dual inhibition of ACC and CD36 for the treatment of nonalcoholic fatty liver disease in mice

Abstract

Dysregulation of hepatic lipid metabolism is a hallmark of nonalcoholic fatty liver disease. Here, we show that dual inhibition of the de novo lipogenesis enzyme, ACC, and hepatic deletion of the fatty acid transporter, CD36, was ineffective for the treatment of NAFLD in mice. This was due to a paradoxical increase in liver triglycerides with CD36 deletion resulting from decreased hepatic triglyceride secretion and increased lipogenic gene expression.