PXD036947-1
PXD036947 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Architecture of the outbred brown fat proteome defines regulators of metabolic physiology |
Description | Obesity 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-11-08 |
AnnouncementXML | Submission_2022-11-08_04:29:20.017.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | HaopengXiao |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | carbamoylated residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-09-22 00:31:35 | ID requested | |
⏵ 1 | 2022-11-08 04:29:20 | announced | |
2 | 2023-11-14 08:09:38 | announced | 2023-11-14: 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
EdwardChouchani | |
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contact affiliation | Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Cell Biology, Harvard Medical School, Boston, MA, USA. |
contact email | EdwardT_Chouchani@DFCI.HARVARD.EDU |
lab head | |
HaopengXiao | |
contact affiliation | Dana-Farber Cancer Institute/Harvard Medical School |
contact email | haopeng_xiao@dfci.harvard.edu |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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