PXD046709

PXD046709 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: brown adipocyte, EPAC

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

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PRIDE project URI

• PRIDE
  1. PXD046709
     1. Label: PRIDE project
     2. Name: EPAC1 enhances energy expenditure by selectively inducing brown and beige adipose tissue growth