Data acquisition and processing were conducted using Analyst 1.6.3 software and the MetWare database (MetWare Biotechnology Co., Ltd., Wuhan, China)
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - reverse-phase","Liquid Chromatography MS - positive - reverse-phase"],"chromatography_protocol":["UPLC-MS/MS Conditions Lipid profiling was performed using an ExionLC AD UPLC system coupled with a QTRAP 6500+ mass spectrometer (Sciex, Framingham, MA, USA). Separation was achieved on a Thermo Accucore C30 column (2.6 μm, 2.1 mm x 100 mm) at 45 °C. The mobile phases were (A) acetonitrile/water (60:40, v/v) and (B) acetonitrile/isopropanol (10:90, v/v), both containing 0.1% formic acid and 10 mM ammonium formate. The gradient elution was performed at a flow rate of 0.35 mL/min.
"],"publication":["Multi-omics reveals the DR5-FXR-CHPT1 axis governs hepatocyte pyroptosis via glycerophospholipid remodeling after major partial hepatectomy."],"submitter_affiliation":["the Third Affiliated Hospital of Sun Yat-sen University"],"submitter_name":["Yongsheng Tang"],"organism_part":["liver"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Lipid Extraction Tissue samples (20 mg) were ground in liquid nitrogen and extracted with 1 mL of solvent mixture (MTBE:MeOH = 3:1, v/v) containing internal standards. After vortexing for 15 min and adding 200 μL of ultrapure water, the mixture was centrifuged at 12,000 rpm for 10 min. The upper organic layer (200 μL)was collected and dried under vacuum. The residue was reconstituted in 200 μL of acetonitrile/isopropanol (ACN:IPA = 1:1, v/v) for LC-MS/MS analysis.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14980"],"author":["Hua Li. Sun Yat-sen University. lihua3@mail.sysu.edu.cn.","Yongsheng Tang. the Third Affiliated Hospital of Sun Yat-sen University. tangysh7@mail2.sysu.edu.cn."],"data_transformation_protocol":["Data acquisition and processing were conducted using Analyst 1.6.3 software and the MetWare database (MetWare Biotechnology Co., Ltd., Wuhan, China)
"],"study_factor":["Group"],"submitter_email":["tangysh7@mail2.sysu.edu.cn"],"sample_collection_protocol":["The samples consist of liver tissues collected from mice that underwent hepatectomy.
"],"omics_type":["Metabolomics"],"study_design":["Mus musculus","Pyroptosis","liver","untargeted analysis","QTRAP 6500+","Post-hepatectomy liver failure (PHLF)","Glycerophospholipid metabolism","Lipidomics","Death receptor 5 (DR5)","Agilent 1290 Infinity LC","Endoplasmic reticulum stress (ERS)","experimental sample","Small-for-size syndrome (SFSS)","Partial hepatectomy (PHx)"],"curator_keywords":["Mus musculus","Pyroptosis","liver","untargeted analysis","QTRAP 6500+","Post-hepatectomy liver failure (PHLF)","Glycerophospholipid metabolism","Lipidomics","Death receptor 5 (DR5)","Agilent 1290 Infinity LC","Endoplasmic reticulum stress (ERS)","experimental sample","Small-for-size syndrome (SFSS)","Partial hepatectomy (PHx)"],"mass_spectrometry_protocol":["The ESI source parameters were set as follows: source temperature 500 °C; ion spray voltage 5500 V (positive) and -4500 V (negative); gas settings GS1 45 psi, GS2 55 psi and curtain gas 35 psi. Lipid quantification was performed in Multiple Reaction Monitoring (MRM) mode.
"],"additional_accession":[]},"is_claimable":false,"name":"Multi-omics reveals the DR5-FXR-CHPT1 axis governs hepatocyte pyroptosis via glycerophospholipid remodeling after major partial hepatectomy","description":"Acute liver injury following major partial hepatectomy (PHx), manifesting as small-for-size syndrome (SFSS) and post-hepatectomy liver failure (PHLF), carries high mortality. However, the key mechanisms underlying irreversible remnant liver injury and cell death remain poorly understood, particularly regarding the contribution of lipid metabolism. To address this, the current study investigates the role of lipid metabolism remodeling in post-hepatectomy hepatocyte injury to identify potential therapeutic targets. By integrating murine graded PHx models and human liver tissues from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedures with multi-omics and machine learning, we identified key regulatory genes. The underlying mechanisms were then validated via in vitro and in vivo genetic manipulation, alongside pharmacological modulation. Our findings reveal that aberrant glycerophospholipid metabolism is the primary driver of endoplasmic reticulum stress (ERS)-mediated pyroptosis in the remnant liver. Specifically, multi-omics analysis combined with machine learning identified death receptor 5 (DR5) as a critical regulator of this process. Mechanistically, DR5 physically impedes the nuclear translocation of the Farnesoid X Receptor (FXR), thereby repressing the transcription of Chpt1 (Cholinephosphotransferase 1). The consequent deficiency in phosphatidylcholine (PC) compromises ER membrane integrity, exacerbating the Unfolded Protein Response and triggering lethal pyroptosis. Strikingly, restoring the DR5-FXR-CHPT1 axis via AAV-mediated DR5 knockdown (DR5-KD), FXR agonists, or exogenous PC supplementation significantly alleviated post-hepatectomy liver injury. Ultimately, this study uncovers a non-canonical metabolic function of DR5 that disrupts ER membrane homeostasis via the FXR-CHPT1 axis, leading to fatal hepatocyte pyroptosis. Targeting this active metabolic reprogramming offers a promising therapeutic strategy to prevent PHLF and SFSS after major PHx.","dates":{"publication":"2026-08-16","submission":"2026-07-08"},"accession":"MTBLS14980","cross_references":{}}