PXD046745

PXD046745 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-07 07:10:37	ID requested
⏵ 1	2025-03-07 03:56:15	announced

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;

submitter keyword: NEFA,Fatty liver, stellate cells

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/03/PXD046745

PRIDE project URI

• PRIDE
  1. PXD046745
     1. Label: PRIDE project
     2. Name: Plasmalemma vesicle-associated protein in hepatic stellate cells is a central regulator of hepatic fatty acid utilization