PXD041439

PXD041439 is an original dataset announced via ProteomeXchange.

Title	Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver
Description	The metabolic functions of the liver are organized spatially in a phenomenon known as zonation. This spatial organization of metabolic functions is linked to the differential exposure of central and portal hepatocytes to either systemic circulation or nutrient-rich blood afferent from the gastrointestinal tract, respectively. The mechanistic target of rapamycin complex 1 (mTORC1) is the central hub of a critical signaling pathway that links cellular metabolism to fluctuations in the levels of nutrients and insulin. To understand how these two signaling cues are integrated in the liver, we have generated mice with constitutive nutrient and insulin signaling to mTORC1 in hepatocytes (RragaGTP/fl; Tsc1fl/fl; Albumin-CreTg mice). Simultaneous activation of nutrient and hormone signaling to mTORC1 results in impaired establishment of the metabolic zonal identity of hepatocytes, a maturation process that takes place within the first weeks after birth. Mechanistically, a decrease in levels of the morphogenic pathway Wnt/β-catenin in hepatocytes and reduced expression of the Wnt2 ligand by liver endothelial cells after birth underlie this impaired wave of hepatocyte maturation. Lack of postnatal establishment of metabolic zonation of the liver is recapitulated in a model of constant supply of nutrients by total parenteral nutrition to neonatal pigs. Collectively, our work shows the critical role of hepatocyte sensing of fluctuations in nutrients and hormones after birth for triggering the latent metabolic zonation program.
HostingRepository	PRIDE
AnnounceDate	2024-03-18
AnnouncementXML	Submission_2024-03-18_07:13:18.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fernando Garcia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-10 07:10:05	ID requested
⏵ 1	2024-03-18 07:13:19	announced

10.1038/S41467-024-46032-1;

submitter keyword: Biological sciences/Cell biology/Cell signalling/Nutrient signalling

Fernando Garcia
contact affiliation	Fernando Garcia Martinez Ph.D. Proteomics & MS Specialist Proteomics Unit, Spanish National Cancer Research Centre (CNIO) Melchor Fernández Almagro 3. E28029 MADRID, SPAIN. Phone +34 912246900 ext 3112
contact email	fgarcia@cnio.es
lab head
Fernando Garcia
contact affiliation	Fernando García Martínez, Ph.D. Proteomics Unit, Spanish National cancer Research Center, CNIO, MADRID, SPAIN
contact email	fgarcia@cnio.es
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/2024/03/PXD041439

PRIDE project URI

• PRIDE
  1. PXD041439
     1. Label: PRIDE project
     2. Name: Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver