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PXD041883

PXD041883 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlemARC1 knockdown protects liver from diet-induced NASH in mouse
DescriptionHuman genetic studies have identified several MARC1 variants as protective against non-alcoholic fatty liver diseases (NAFLD). The MARC1 variants are associated with reduced lipid profiles, liver enzymes, and liver-related mortality. However, the role of mitochondrial amidoxime reducing component 1 (mARC1), encoded by MARC1, in NAFLD is still unknown and the therapeutic potential of this target has never been developed. Given that mARC1 is mainly expressed in hepatocytes, we developed an N-acetylgalactosamine conjugated mouse mARC1 siRNA to address this. In ob/ob mice, knockdown of mARC1 in mouse hepatocytes resulted in decreased liver weight, serum lipid enzymes, low-density lipoprotein cholesterol, and liver triglycerides. Loss of mARC1 also improved the lipid profiles and attenuated liver pathological changes in two diet-induced nonalcoholic steatohepatitis (NASH) mouse models. A comprehensive analysis of mARC1-deficient liver in NASH by metabolomics, proteomics, and lipidomics showed that mARC1 knockdown partially restored metabolites and lipids altered by diets. Taken together, loss of mARC1 protects mouse liver from NASH, suggesting a potential therapeutic approach of NASH by downregulation of mARC1 in hepatocytes.
HostingRepositoryMassIVE
AnnounceDate2024-05-09
AnnouncementXMLSubmission_2024-05-09_13:21:08.430.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMatt Rardin
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListOxidation; Carbamidomethyl
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-04-28 15:37:33ID requested
12024-05-09 13:21:08announced
Publication List
no publication
Keyword List
submitter keyword: MARC1, NASH, TMT
Contact List
Matthew Rardin
contact affiliationAmgen
contact emailmrardin@amgen.com
lab head
Matt Rardin
contact affiliationAmgen
contact emailmrardin@amgen.com
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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