PXD057035

PXD057035 is an original dataset announced via ProteomeXchange.

Title	Trifluoroacetate reduces plasma lipid levels and the development of atherosclerosis in mice
Description	Here we show that trifluoroacetate (TFA), previously assumed to be an innocuous counterion to cationic amino acid side chains (Lys, Arg, His, N-terminal amines) found in countless synthetic bioactive peptides and a few FDA-approved therapeutics, is in fact bioactive– TFA causes dramatic biological effects in multiple strains of mice and cultured human and rat liver cells. In high fat diet (HFD)-fed low density lipoprotein receptor-null (LDLr-/-) mice, TFA induces reductions in plasma cholesterol and triglycerides levels, following either oral or intraperitoneal administration. These physiological effects were observed with TFA alone, or with TFA present as a counterion of a variety of short, unrelated synthetic peptide sequences. Furthermore, 10-wk daily oral administration of TFA reduced the development of atherosclerotic lesions in the LDLr-/- mice. Mechanistic investigations including RNA-seq, confocal microscopy, western blotting, metabolomics, proteomics, pharmacokinetics, and biochemical assays indicated that TFA induces peroxisome proliferation by activating peroxisome proliferator-activated receptor (PPAR)-alpha. We confirmed that TFA also caused peroxisome proliferation and downstream phenotypic effects in cultured human and rat liver cells, wild-type C57/Bl mice, and apolipoprotein E-null (apoE-/-) mice, leading to anti-atherosclerotic effects in the latter strain. Given that TFA is present as counterion in many peptides employed in early research and development settings, these findings raise the possibility that TFA may be confounding or contributing to phenotypic changes observed in many studies involving peptides. Moreover, TFA is a persistent environmental contaminant that is found at high levels in humans relative to other polyfluoroalkyl substances (PFAS), and is a major metabolite following treatment of patients with common inhaled anesthetics, suggesting that the biological effects reported here could be relevant to human health.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-12_17:01:37.728.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Louis Conway
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-21 18:40:09	ID requested
⏵ 1	2025-03-12 17:01:38	announced

10.1101/2025.03.06.641713;

submitter keyword: atherosclerosis, peroxisome, cholesterol, peptide, trifluoroacetate

Christopher G Parker
contact affiliation	Department of Chemistry, The Scripps Research Institute
contact email	cparker@scripps.edu
lab head
Louis Conway
contact affiliation	Scripps Research
contact email	lconway@scripps.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/2025/03/PXD057035

PRIDE project URI

• PRIDE
  1. PXD057035
     1. Label: PRIDE project
     2. Name: Trifluoroacetate reduces plasma lipid levels and the development of atherosclerosis in mice