The hepatoprotective benefits of semaglutide in MASH require the intrahepatic endothelial GLP-1 receptor

GLP-1R expression in the liver is restricted to non-parenchymal cells, but its detection by conventional single-cell RNA sequencing is limited due to low transcript abundance. We performed GEM-X Flex-seq (10x Genomics) single-cell RNA sequencing on liver single-cell suspensions from wild-type C57BL/6J mice fed a standard chow diet, a choline-deficient high-fat diet (CDHFD), or CDHFD with semaglutide treatment.

This dataset enables cell type-resolved mapping of Glp1r expression across the hepatic niche and characterization of transcriptomic changes associated with semaglutide treatment, revealing pericentral liver sinusoidal endothelial cells (LSECs) as direct targets mediating weight loss-independent improvements in hepatic inflammation, fibrosis, and immune remodeling.