PXD019755-2

PXD019755 is an original dataset announced via ProteomeXchange.

Title	Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
Description	Excessive glucose production in the liver is a key factor in the hyperglycemia observed in diabetes mellitus type 2. It is generally agreed to result from an increase in hepatic gluconeogenesis. Considerable attention has been devoted to the transcriptional regulation of key gluconeogenic enzymes, but much less is known about the regulation of amino-acid catabolism, which generates gluconeogenic substrates. Here, we highlight a novel role of LKB1 in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect was observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion was associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic and pharmacological approaches, we identified the aminotransferases and specifically, Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis. The present dataset is from the phosphoproteomic analysis of the refed mice in a study where a global quantitative analysis ( PXD013478 ) is also described in the same publication.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:15:57.073.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	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-15 02:47:57	ID requested
1	2020-11-30 23:39:40	announced
⏵ 2	2024-10-22 05:15:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: gluconeogenesis, phosphoproteome, sarcopenia, liver, cachexia, Q-exactive, label-free quantification, amino acids,LKB1, orbitrap Fusion, refed mice

Christine PERRET
contact affiliation	Inserm U1016, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 PARIS, FRANCE.
contact email	christine.perret@inserm.fr
lab head
François GUILLONNEAU
contact affiliation	ICO Angers
contact email	francois.guillonneau@parisdescartes.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019755
     1. Label: PRIDE project
     2. Name: Lkb1 suppresses amino acid-driven gluconeogenesis in the liver