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Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein [snRNA-seq]

GSE246087 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/03/04 Platform GPL24247
Summary
The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification to di- and triacylglycerols shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy we localized HSC PLVAP to caveolae residing along the sinusoidal lumen supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.
Published in
Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein
Hansen D, Jensen JER, Andersen CAT et al. · Cell metabolism 2025 · PMID 40037362 · doi:10.1016/j.cmet.2025.01.022
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Direct links to NCBI, no account and no request form: the whole study as GSE246087_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1031322 and SRA study SRP468037. Searching any of these in the dataset finder brings you back here.

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