Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice.
10.1016/j.jpha.2025.101273
- Author:
Yuxuan CHEN
1
;
Chendong LIU
1
;
Qian YANG
1
;
Jingtao YANG
1
;
He ZHANG
2
;
Yong ZHANG
3
;
Yanruyu FENG
1
;
Jiaqi LIU
1
;
Lian LI
1
;
Dapeng LI
1
Author Information
1. Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
2. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
3. Department of Nephrology, Institutes for Systems Genetics, West China Hospital, Sichuan University, Chengdu, 610041, China.
- Publication Type:Journal Article
- Keywords:
Glycoproteomics;
Hydrogel-based delivery;
Liraglutide;
Metabolic dysfunction-associated steatotic liver disease;
N-glycosylation site;
Proteomics
- From:
Journal of Pharmaceutical Analysis
2025;15(11):101273-101273
- CountryChina
- Language:English
-
Abstract:
Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.
