PXD046745 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Plasmalemma vesicle-associated protein in hepatic stellate cells is a central regulator of hepatic fatty acid utilization |
Description | The liver is essential for fatty acid utilization during fasting. Fatty acids released by lipolysis from adipose tissue during fasting are taken up from the blood by hepatocytes and esterified as triacylglycerols for oxidative metabolization and ketogenesis. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, transport of non-esterified fatty acids (NEFAs) from the liver sinusoidal lumen to the hepatocyte is not. Here, we show that murine hepatic stellate cells (HSCs), enveloping the liver sinusoids as pericytes, and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic NEFA uptake during fasting. HSC-specific ablation of PLVAP suppresses hepatocyte fatty acid esterification to di- and triacylglycerols along with fasting fatty acid utilization and ketogenesis. Consistently, single cell-resolved transcriptomics further revealed severe perturbation of hepatocyte gene programs governing normal fatty acid handling, oxidation, and ketogenesis. By super-resolution microscopy we localized HSC PLVAP to caveolae residing along the sinusoidal lumen strongly supporting a role for PLVAP in caveolar transcytosis of NEFAs across HSCs and hence the sinusoid wall as rate-limiting for hepatic fatty acid utilization during fasting. This was supported by a similar decline in neutral lipid droplet formation in livers of fasting Caveolin-1 knockout mice. Altogether, our study shows vital roles for PLVAP and for HSCs in normal fasting metabolism of liver. |
HostingRepository | PRIDE |
AnnounceDate | 2025-03-07 |
AnnouncementXML | Submission_2025-03-07_03:56:14.763.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Vyacheslav Akimov |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-07 07:10:37 | ID requested | |
⏵ 1 | 2025-03-07 03:56:15 | announced | |
Publication List
Hansen D, Jensen JER, Andersen CAT, Jakobsgaard PR, Havelund J, Lauritsen L, Mandacaru S, Siersbaek M, Shackleton OL, Inoue H, Brewer JR, Schwabe RF, Blagoev B, F, æ, rgeman NJ, Salmi M, Ravnskjaer K, Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein. Cell Metab, 37(4):971-986.e8(2025) [pubmed] |
10.1016/j.cmet.2025.01.022; |
Keyword List
submitter keyword: NEFA,Fatty liver, stellate cells |
Contact List
Blagoy Blagoev |
contact affiliation | Department of Biochemistry and Molecular Biology, University of Southern Denmark |
contact email | bab@bmb.sdu.dk |
lab head | |
Vyacheslav Akimov |
contact affiliation | Center for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark |
contact email | akimov@bmb.sdu.dk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046745
- Label: PRIDE project
- Name: Plasmalemma vesicle-associated protein in hepatic stellate cells is a central regulator of hepatic fatty acid utilization