PXD075389

PXD075389 is an original dataset announced via ProteomeXchange.

Title	GPER1 as a therapeutic target in MASLD: evidence for steatosis attenuation by agonist G1 in preclinical models
Description	Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver-related morbidity and mortality. Premenopausal women have a lower MASLD risk than postmenopausal women. G protein-coupled estrogen receptor 1 (GPER1) exerts hepatic protective effects, and GPER1 specific agonist (G1) has shown preclinical potential in improving metabolic disorders. However, clinical studies on G1’s metabolic benefits and GPER1’s clinical relevance in human liver tissue remain unclear. This study aims to bridge basic and clinical research by validating G1’s efficacy in ameliorating MASLD-related hepatic steatosis, exploring its molecular mechanisms, and clarifying GPER1’s association with human MASLD. Methods We investigated the expression of GPER1 in human liver tissue and its correlation with the severity of steatosis. The function of GPER1 was validated both in vitro (using a free fatty acid-induced hepatocyte steatosis model treated with the GPER1 agonist G1 or antagonist G15) and in vivo, with assessments of lipid metabolism-related genes, reactive oxygen species, and apoptosis. GPER1-associated proteins were identified through proteomic sequencing and co-immunoprecipitation. Results GPER1 is lowly expressed in MASLD patients, negatively correlating with steatosis severity. G1 upregulates GPER1, alleviates hepatocyte steatosis and lipid deposition, modulates lipid metabolism-related proteins, ameliorates hepatic steatosis, and interacts with GAIP-interacting protein C-terminal 1 (GIPC1). G15 antagonizes these beneficial effects. Conclusions Based on clinical data, this study shows that low GPER1 expression correlates closely with hepatic steatosis in MASLD. The GPER1 agonist G1 ameliorates hepatic steatosis via multiple GPER1-dependent mechanisms, including regulating lipid metabolism, suppressing oxidative stress, and reducing apoptosis. Notably, GIPC1 may be involved in the GPER1-mediated regulatory pathway, and its role in this context merits further investigation.
HostingRepository	iProX
AnnounceDate	2026-03-09
AnnouncementXML	Submission_2026-03-09_01:55:46.685.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yifang Li
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-09 01:55:17	ID requested
⏵ 1	2026-03-09 01:55:47	announced

Dataset with its publication pending

submitter keyword: G protein-coupled estrogen receptor 1 (GPER1), GPER1 antagonist (G15), GPER1-specific agonist (G1), Hepatic steatosis, Metabolic dysfunction-associated steatotic liver disease (MASLD)

Jian Jiao
contact affiliation	China-Japan Union Hospital of Jilin University
contact email	jjian@jlu.edu.cn
lab head
Yifang Li
contact affiliation	China-Japan Union Hospital of Jilin University
contact email	yifang22@mails.jlu.edu.cn
dataset submitter

iProX dataset URI