PXD046709 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | EPAC1 enhances energy expenditure by selectively inducing brown and beige adipose tissue growth |
Description | Brown 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:13:54.271.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Natalie Krahmer |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-06 13:36:14 | ID requested | |
1 | 2023-11-11 02:58:12 | announced | |
⏵ 2 | 2024-10-22 06:13:54 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: brown adipocyte, EPAC |
Contact List
Natalie Krahmer |
contact affiliation | Helmholtz Diabetes Center Munich |
contact email | natalie.krahmer@helmholtz-munich.de |
lab head | |
Natalie Krahmer |
contact affiliation | Helmholtz Center Munich |
contact email | natalie.krahmer@helmholtz-muenchen.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046709
- Label: PRIDE project
- Name: EPAC1 enhances energy expenditure by selectively inducing brown and beige adipose tissue growth