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PXD046709

PXD046709 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEPAC1 enhances energy expenditure by selectively inducing brown and beige adipose tissue growth
DescriptionBrown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure (EE) and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show by phosphoproteomics that cAMP activates distinct signaling pathways in brown progenitors, with the cAMP-EPAC1 axis enhancing proliferation and differentiation of thermogenic but not white adipocytes. Further analysis revealed that a specific subpopulation of preadipocytes that are PDGFRα-positive express EPAC1. In vivo, pharmacological activation of EPAC1 enhances BAT growth and browning of white fat, leading to increased EE and reduced diet-induced adiposity. In contrast, mice lacking EPAC1 in PDGFRα-positive preadipocytes show the opposite phenotype. Importantly, EPAC1 activation enhances proliferation and differentiation of human brown adipocytes and human brown fat organoids. Interestingly, a coding variant in EPAC1 that positively correlates with BMI abolishes norepinephrine-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and EE to combat metabolic diseases.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:13:54.271.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNatalie Krahmer
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-06 13:36:14ID requested
12023-11-11 02:58:12announced
22024-10-22 06:13:54announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: brown adipocyte, EPAC
Contact List
Natalie Krahmer
contact affiliationHelmholtz Diabetes Center Munich
contact emailnatalie.krahmer@helmholtz-munich.de
lab head
Natalie Krahmer
contact affiliationHelmholtz Center Munich
contact emailnatalie.krahmer@helmholtz-muenchen.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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