PXD009262

PXD009262 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: mouse, liver, mitochondria, label-free

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

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PRIDE project URI

• PRIDE
  1. PXD009262
     1. Label: PRIDE project
     2. Name: Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis