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

GSE325222 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/04/14 Platform GPL34328
Summary
GLP-1 receptor agonists such as semaglutide improve metabolic dysfunction-associated liver disease (MASLD), yet the hepatic cell types mediating these effects remain unclear. 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.
Published in
The weight-loss-independent hepatoprotective benefits of semaglutide are orchestrated by intrahepatic sinusoidal endothelial GLP-1 receptors
Gonzalez-Rellan MJ, Riobello C, Fang S et al. · Cell metabolism 2026 · PMID 41985454 · doi:10.1016/j.cmet.2026.03.011
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Direct links to NCBI, no account and no request form: the whole study as GSE325222_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1439199 and SRA study SRP684745. Searching any of these in the dataset finder brings you back here.

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