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PXD036947

PXD036947 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleArchitecture of the outbred brown fat proteome defines regulators of metabolic physiology
DescriptionObesity is a polygenic disorder with variable penetrance in the general population. Brown adipose tissue (BAT) is a major regulator of energy expenditure and metabolic physiology due to a specialized proteome that orchestrates futile metabolic cycles, which could be leveraged to treat obesity. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited understanding of generalizable mechanisms of BAT regulation over metabolism. Here we perform deep quantitative multiplexed proteomics of BAT across a cohort of 163 genetically defined Diversity Outbred (DO) mice, a model that parallels the genetic and phenotypic variation found in the human population. Leveraging the high variation afforded by this model, we define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. In doing so, we assign novel co-operative functions to 2,578 proteins with 780 established protein networks. We demonstrate that this analytic framework enables systematic discovery of regulators of BAT function, exemplified by uncovering SFXN5 and LETMD1 as modulators of UCP1-dependent thermogenesis. We also identify 638 proteins that underlie protection from, or sensitivity to, at least one parameter of metabolic disease. From this basis, we identify the Na+/K+- ATPase α2 subunit as an inhibitor of BAT energy expenditure, that increases adiposity through antagonism of calcium influx-dependent activation of thermogenic effectors. We provide this Outbred Proteomic Architecture as a resource for understanding conserved mechanisms of BAT regulation over metabolic physiology.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:09:34.929.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHaopeng Xiao
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListcarbamoylated residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-22 00:31:35ID requested
12022-11-08 04:29:20announced
22023-11-14 08:09:38announced2023-11-14: Updated project metadata.
Publication List
Xiao H, Bozi LHM, Sun Y, Riley CL, Philip VM, Chen M, Li J, Zhang T, Mills EL, Emont MP, Sun W, Reddy A, Garrity R, Long J, Becher T, Vitas LP, Laznik-Bogoslavski D, Ordonez M, Liu X, Chen X, Wang Y, Liu W, Tran N, Liu Y, Zhang Y, Cypess AM, White AP, He Y, Deng R, Sch, ö, der H, Paulo JA, Jedrychowski MP, Banks AS, Tseng YH, Cohen P, Tsai LT, Rosen ED, Klein S, Chondronikola M, McAllister FE, Van Bruggen N, Huttlin EL, Spiegelman BM, Churchill GA, Gygi SP, Chouchani ET, Architecture of the outbred brown fat proteome defines regulators of metabolic physiology. Cell, 185(24):4654-4673.e28(2022) [pubmed]
Keyword List
submitter keyword: diversity outbred, QTL, physiology, metabolic disease, network, proteome,obesity, phenotype
Contact List
Edward Chouchani
contact affiliationDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
contact emailEdwardT_Chouchani@DFCI.HARVARD.EDU
lab head
Haopeng Xiao
contact affiliationDana-Farber Cancer Institute/Harvard Medical School
contact emailhaopeng_xiao@dfci.harvard.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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