PXD053061-2

PXD053061 is an original dataset announced via ProteomeXchange.

Title	LGR signaling mediates muscle-adipose tissue crosstalk and protects against diet-induced insulin resistance
Description	Obesity impairs tissue insulin sensitivity and signaling, promoting type-2 diabetes. Although improving insulin signaling is key to reversing diabetes, the multi-organ mechanisms regulating this process are poorly defined. We screened the secretome and receptome in Drosophila to identify the hormonal crosstalk affecting diet-induced insulin resistance and obesity. We discovered a complex interplay between muscle, neuronal, and adipose tissues, mediated by Bone Morphogenetic Protein (BMP) signaling and the hormone Bursicon, that enhances insulin signaling and sugar tolerance. Muscle-derived BMP signaling, induced by sugar, governs neuronal Bursicon signaling. Bursicon, through its receptor Rickets, a Leucine-rich-repeat-containing G-protein coupled receptor (LGR), improves insulin secretion and insulin sensitivity in adipose tissue, mitigating hyperglycemia. In mouse adipocytes, loss of the Rickets ortholog LGR4 blunts insulin responses, showing an essential role of LGR4 in adipocyte insulin sensitivity. Our findings reveal a muscle-neuronal-fat-tissue axis driving metabolic adaptation to high-sugar conditions, identifying LGR4 as a critical mediator in this regulatory network.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:45.029.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin R. Larsen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-12 23:40:14	ID requested
1	2024-06-27 09:22:59	announced
⏵ 2	2024-10-22 06:47:45	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Phosphoproteomics, Muscle-adipose tissue crosstalk, LGR,Insulin resistance, T2D

Kim Rewitz
contact affiliation	Department of Biology, University of Copenhagen, 2100 Copenhagen O, Denmark
contact email	Kim.Rewitz@bio.ku.dk
lab head
Martin R. Larsen
contact affiliation	University of Southern Denmark
contact email	mrl@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/2024/06/PXD053061

PRIDE project URI

• PRIDE
  1. PXD053061
     1. Label: PRIDE project
     2. Name: LGR signaling mediates muscle-adipose tissue crosstalk and protects against diet-induced insulin resistance