Eric M Desjardins, Jianhan Wu, Declan C T Lavoie, Elham Ahmadi, Logan K Townsend, Marisa R Morrow, Dongdong Wang, Evangelia E Tsakiridis, Battsetseg Batchuluun, Russta Fayyazi, Jacek M Kwiecien, Theodoros Tsakiridis, James S V Lally, Guillaume Paré, Stephen L Pinkosky, Gregory R Steinberg
Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH is ATP citrate lyase (ACLY). In mice, inhibition of ACLY reduces liver steatosis, ballooning, and fibrosis and inhibits activation of hepatic stellate cells. Glucagon-like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance, and steatosis without improving fibrosis. Here, we find that combining an inhibitor of liver ACLY, bempedoic acid, and the GLP-1R agonist liraglutide reduces liver steatosis, hepatocellular ballooning, and hepatic fibrosis in a mouse model of NASH...
September 19, 2023: Cell reports medicine