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PXD046745

PXD046745 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePlasmalemma vesicle-associated protein in hepatic stellate cells is a central regulator of hepatic fatty acid utilization
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2025-03-07
AnnouncementXMLSubmission_2025-03-07_03:56:14.763.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVyacheslav Akimov
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-07 07:10:37ID requested
12025-03-07 03:56:15announced
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 affiliationDepartment of Biochemistry and Molecular Biology, University of Southern Denmark
contact emailbab@bmb.sdu.dk
lab head
Vyacheslav Akimov
contact affiliationCenter for Experimental BioInformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
contact emailakimov@bmb.sdu.dk
dataset submitter
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