PXD013478

PXD013478 is an original dataset announced via ProteomeXchange.

Title	LKB1 is a suppressor of amino acid-driven gluconeogenesis in the liver
Description	Excessive hepatic glucose production is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus. It is widely accepted that it is due to an increase in hepatic gluconeogenesis. While much attention has been devoted to the transcriptional regulation of key gluconeogenic enzymes, much less is known about the regulation of amino acid catabolism that provides gluconeogenic substrates. Here, we emphasize a novel role of LKB1 in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have increased hepatic amino acid catabolism for gluconeogenesis. This occurred during fasting, as well as during the postprandial period, identifying Lkb1 as a critical suppressor of hepatic postprandial gluconeogenesis. Hepatic Lkb1 deletion was also associated with severe alterations in whole body metabolism leading to decreased lean body mass deposition on MRI analysis and, at a longer term, cachexia and sarcopenia as a consequence of the diversion of amino acids for liver metabolism at the expense of muscle. Using genetic and pharmacological approaches, we identified the aminotransferases and Agxt and as critical effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
HostingRepository	PRIDE
AnnounceDate	2020-12-01
AnnouncementXML	Submission_2020-12-04_00:57:43.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-12 02:31:40	ID requested
1	2020-11-30 23:56:40	announced
⏵ 2	2020-12-04 00:57:44	announced	2020-12-04: Updated publication reference for PubMed record(s): 33257663.

Just PA, Charawi S, Denis RGP, Savall M, Traore M, Foretz M, Bastu S, Magassa S, Senni N, Sohier P, Wursmer M, Vasseur-Cognet M, Schmitt A, Le Gall M, Leduc M, Guillonneau F, De Bandt JP, Mayeux P, Romagnolo B, Luquet S, Bossard P, Perret C, Lkb1 suppresses amino acid-driven gluconeogenesis in the liver. Nat Commun, 11(1):6127(2020) [pubmed]

submitter keyword: LKB1, Mus musculus, gluconeogenesis, liver, insulin, amino acids, sarcopenia, Q-exactive, label-free, maxquant

Dr Christine Perret
contact affiliation	INSERM, U1016, Institut Cochin, F-75014 Paris, France. CNRS, UMR8104, F-75014 Paris, France. Université de Paris, Université Paris Descartes, F-75014 Paris, France.
contact email	christine.perret@inserm.fr
lab head
François GUILLONNEAU
contact affiliation	3P5 Université Paris Descartes
contact email	francois.guillonneau@parisdescartes.fr
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/2020/12/PXD013478

PRIDE project URI

• PRIDE
  1. PXD013478
     1. Label: PRIDE project
     2. Name: LKB1 is a suppressor of amino acid-driven gluconeogenesis in the liver