Inhibition of DHCR24 activates LXRα to ameliorate hepatic steatosis and inflammation

ABSTRACT: Liver X receptor (LXR) agonism has theoretical potential for treating NAFLD/NASH but synthetic agonists induce hyperlipidemia in preclinical models. Desmosterol, which is converted by Δ24-dehydrocholesterol reductase (DHCR24) into cholesterol, is a potent endogenous LXR agonist with anti-inflammatory properties. We aimed to investigate the effects of DHCR24 inhibition on NAFLD/NASH development. Here, by using APOE*3-Leiden.CETP mice, a well-established translational model that develops diet-induced human-like NAFLD/NASH characteristics, we report that SH42, a publishedDHCR24 inhibitor, markedly increases desmosterol levels in liver and plasma, reduces hepatic lipid content and the steatosis score, and decreases plasma fatty acid and cholesteryl ester concentrations. Flow cytometry showed t

SUBMITTER: Dr. Enchen Zhou Zhou 

PROVIDER: S-SCDT-10_15252-EMMM_202216845 | biostudies-other |

REPOSITORIES: biostudies-other