PXD046255

PXD046255 is an original dataset announced via ProteomeXchange.

Title	Liver proteiomic analysis on westeren diet fed mice under oral supplementation of indole-3-acetate
Description	Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is growing evidence that dysbiosis of the intestinal microbiota and disruption of microbiota-host interactions contribute to the pathology of NAFLD. We previously demonstrated that gut microbiota derived tryptophan metabolite indole-3-acetate (I3A) was decreased in both cecum and liver of high-fat diet-fed mice and attenuated the expression of inflammatory cytokines in macrophages and TNF-a and fatty acid induced inflammatory responses in an aryl-hydrocarbon receptor (AhR) dependent manner in hepatocytes. In this study, we investigated the effect of orally administered I3A in a mouse model of diet induced NAFLD. Western diet (WD)-fed mice given sugar water (SW) with I3A showed dramatically decreased serum ALT, hepatic TG, liver steatosis, hepatocyte ballooning, lobular inflammation, and hepatic production of inflammatory cytokines, compared to WD-fed mice given only SW. Metagenomic analysis show that I3A administration did not significantly modify the intestinal microbiome, suggesting that I3A’s beneficial effects likely reflect the metabolite’s direct actions on the liver. Administration of I3A partially reversed WD induced alterations of liver metabolome and proteome, notably, decreasing expression of several enzymes in hepatic lipogenesis and β- oxidation. Mechanistically, we also show that AMP-activated protein kinase (AMPK) mediates the anti-inflammatory effects of I3A in macrophages. The potency of I3A in alleviating liver steatosis and inflammation clearly demonstrates its potential as a therapeutic modality for preventing the progression of steatosis to NASH.
HostingRepository	PRIDE
AnnounceDate	2024-02-23
AnnouncementXML	Submission_2024-02-22_16:32:56.278.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karin Yanagi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-20 00:06:40	ID requested
⏵ 1	2024-02-22 16:32:56	announced

10.7554/ELIFE.87458.2;

submitter keyword: Mouse, LC-MS, Liver

Kyongbum Lee;
contact affiliation	Department of Chemical and Biological Engineering, Tufts University; Medford, MA 02155, USA Artie McFerrin Department of Chemical Engineering, Texas A&M University; College Station, TX 77843, USA, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas Health Science Center, Texas A&M University; Bryan, TX, USA
contact email	kyongbum.lee@tufts.edu
lab head
Karin Yanagi
contact affiliation	Tufts University
contact email	karin.yanagi@tufts.edu
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/2024/02/PXD046255

PRIDE project URI

• PRIDE
  1. PXD046255
     1. Label: PRIDE project
     2. Name: Liver proteiomic analysis on westeren diet fed mice under oral supplementation of indole-3-acetate