PXD077702

PXD077702 is an original dataset announced via ProteomeXchange.

Title	Butyrate Counteracts Maternal Obesity-Induced Cardiac Defects by Promoting PLEKHG3-Actin Binding
Description	Maternal obesity increases the risk of abnormal cardiac development during gestation. However, the underlying metabolic determinants contributing to these defects remain insufficiently understood. In this study, reduced butyrate was identified in HFD-fed mice and their embryos, accompanied by fetal cardiac abnormalities, including ventricular wall thickening, sarcomere elongation, and myofibril disorganization. These abnormalities could be rescued by butyrate supplementation. For in vitro verification in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and organoids, butyrate effectively restored palmitate-induced contractile dysfunction and myofibrillar disarray. Mechanistically, drug affinity-responsive target stability (DARTS) assays and molecular docking analyses identified pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3), which enables actin binding activity, as a direct target of butyrate. Butyrate binding enhanced the interaction between PLEKHG3 and F-Actin, thereby promoting contractility and orderly assembly of myofibrils. Conversely, loss-of-function mutation (Q175A) in PLEKHG3 disrupted PLEKHG3/F-Actin binding and abrogated protective effects of butyrate. Collectively, these findings reveal that butyrate ameliorates obesity-induced embryonic cardiac defects by modulating PLEKHG3/F-Actin axis, highlighting its potential as a therapeutic metabolite for mitigating cardiac abnormalities associated with maternal obesity.
HostingRepository	iProX
AnnounceDate	2026-04-27
AnnouncementXML	Submission_2026-08-24_02:39:30.830.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanqi Xia
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-27 23:36:04	ID requested
⏵ 1	2026-08-24 02:39:31	announced

Dataset with its publication pending

submitter keyword: butyrate, cardiac development, maternal obesity, PLEKHG3

Guolian Ding
contact affiliation	Obstetrics and Gynecology Hospital, Fudan University
contact email	dingguolian@fudan.edu.cn
lab head
Yanqi Xia
contact affiliation	Obstetrics and Gynecology Hospital, Fudan University
contact email	25111250025@m.fudan.edu.cn
dataset submitter

iProX dataset URI