PXD023471

PXD023471 is an original dataset announced via ProteomeXchange.

Title	Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Description	miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33–knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases.
HostingRepository	PRIDE
AnnounceDate	2023-11-07
AnnouncementXML	Submission_2023-11-07_05:32:39.599.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SeanBurnap
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-08 02:49:44	ID requested
1	2021-02-11 09:53:46	announced
⏵ 2	2023-11-07 05:32:40	announced	2023-11-07: Updated project metadata.

Price NL, Zhang X, Fern, á, ndez-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfr, á, n-Duque A, Aryal B, Mayr M, Su, á, rez Y, Fern, á, ndez-Hernando C, Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proc Natl Acad Sci U S A, 118(5):(2021) [pubmed]

submitter keyword: Mouse plasma

ManuelMayr
contact affiliation	King's British Hear Foundation Centre, King's College London
contact email	manuel.mayr@kcl.ac.uk
lab head
SeanBurnap
contact affiliation	King's College London
contact email	sean.a.burnap@kcl.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/02/PXD023471

PRIDE project URI

• PRIDE
  1. PXD023471
     1. Label: PRIDE project
     2. Name: Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis