PXD009262 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis |
Description | Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans. |
HostingRepository | PRIDE |
AnnounceDate | 2018-07-12 |
AnnouncementXML | Submission_2019-06-17_03:26:46.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Danielle Swaney |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-03-20 02:32:01 | ID requested | |
1 | 2018-07-12 03:59:13 | announced | |
⏵ 2 | 2019-06-17 03:26:47 | announced | Updated publication reference for PubMed record(s): 30030465. |
Publication List
Paulo E, Wu D, Wang Y, Zhang Y, Wu Y, Swaney DL, Soucheray M, Jimenez-Morales D, Chawla A, Krogan NJ, Wang B, Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis. Sci Rep, 8(1):11001(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: mouse, liver, mitochondria, label-free |
Contact List
Danielle Swaney |
contact affiliation | Cellular and Molecular Pharmacology, Quantitative Biosciences Institute, Gladstone Institutes, University of California San Francisco, CA, USA |
contact email | danielle.swaney@ucsf.edu |
lab head | |
Danielle Swaney |
contact affiliation | UCSF |
contact email | daniswan@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD009262
- Label: PRIDE project
- Name: Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis