Lipid identification was performed using Thermo Scientific LipidSearch v4.1. Product ion mode was used for identification. The mass tolerance for precursor and product ions was set to 5 ppm, and the response threshold was set to 5.0% relative response deviation of product ions. Peak areas of identified lipids were used for quantification with a mass tolerance of 5 ppm. The filter settings included top rank, all isomer peak, fatty acid priority, M-score of 5.0, and c-score of 2.0. Identification levels A, B, C, and D were retained. Positive ion adducts included [M+H]+, [M+NH4]+, and [M+Na]+. Negative ion adducts included [M-H]-, [M-2H]-, and [M-HCOO]-. Lipids not marked as rejected after peak alignment were retained for downstream analysis.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - negative - reverse-phase","Liquid Chromatography MS - positive - reverse-phase"],"chromatography_protocol":["Lipid separation was performed using a Waters 2D UPLC system equipped with an ACQUITY UPLC CSH C18 column (1.7 µm, 2.1 × 100 mm, Waters). The column oven was maintained at 55°C, the flow rate was 0.35 mL/min, and the injection volume was 5 µL. For positive ion mode, mobile phase A was 60% acetonitrile aqueous solution containing 0.1% formic acid and 10 mM ammonium formate, and mobile phase B was 10% acetonitrile aqueous solution/90% isopropanol containing 0.1% formic acid and 10 mM ammonium formate. For negative ion mode, mobile phase A was 60% acetonitrile aqueous solution containing 10 mM ammonium formate, and mobile phase B was 10% acetonitrile aqueous solution/90% isopropanol containing 10 mM ammonium formate. The gradient was: 0–2 min, 40–43% B; 2–2.1 min, 43–50% B; 2.1–7 min, 50–54% B; 7–7.1 min, 54–70% B; 7.1–13 min, 70–99% B; 13–13.1 min, 99–40% B; 13.1–15 min, 40% B.
"],"publication":["Severe hyperchylomicronemia sensitizes the heart to pathological remodeling: evidence from GPIHBP1 deficient mice."],"submitter_affiliation":["Peking University"],"submitter_name":["rui fan"],"organism_part":["heart"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Approximately 25 mg of tissue was weighed into a 1.5 mL Eppendorf tube. Lipids were extracted by adding 800 µL of extraction solvent consisting of dichloromethane/methanol (3:1, v/v, pre-cooled at -20°C), 10 µL of SPLASH internal standards solution, and two small steel balls. Samples were homogenized using a tissue grinder at 50 Hz for 5 min, sonicated in a 4°C water bath for 10 min, and incubated at -20°C for 1 h. Samples were then centrifuged at 4°C for 15 min at 25,000 rpm. A total of 600 µL supernatant was collected, dried, and reconstituted in 200 µL of isopropanol/acetonitrile/water (2:1:1). The reconstituted sample was vortexed for 1 min, sonicated at 4°C for 10 min, and centrifuged at 4°C for 15 min at 25,000 rpm. The supernatant was transferred to an LC-MS vial. Quality control samples were prepared by pooling 20 µL from each sample.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14749"],"author":["jiaowei liao. First Affiliated Hospital of Dalian Medical University. liaojiawei@bjmu.edu.cn.","rui fan. First Affiliated Hospital of Dalian Medical University. fanrui1225@126.com."],"data_transformation_protocol":["Raw LC-MS/MS data files were processed using Thermo Scientific LipidSearch v4.1 for lipid identification, peak extraction, and peak alignment. The original data exported from LipidSearch were imported into metaX for preprocessing and statistical analysis. Lipid molecules missing in more than 50% of QC samples and more than 80% of experimental samples were removed. Missing values were imputed using the K-nearest neighbor algorithm. Probabilistic quotient normalization was applied to normalize the data and obtain relative peak areas. Lipid molecules with a coefficient of variation greater than 30% in QC samples were removed.
"],"study_factor":["Genotype"],"submitter_email":["fanrui1225@126.com"],"sample_collection_protocol":["Heart tissue samples were collected from 10-month-old male Gpihbp1 knockout mice and wild-type littermate controls. After collection, samples were immediately frozen in liquid nitrogen and stored at -80°C until lipid extraction. The sample set included 4 control samples and 4 Gpihbp1 knockout samples.
"],"omics_type":["Metabolomics"],"study_design":["Mus musculus","untargeted analysis","Lipidomics","heart","genotype design","experimental sample","Waters 2D UPLC system","lipid profiling assay","Thermo Scientific Q Exactive","Thermo Scientific Q Exactive HF","hyperchylomicronemia","Waters ACQUITY UPC2 System","case control design"],"curator_keywords":["Mus musculus","untargeted analysis","Lipidomics","genotype design","heart","experimental sample","Waters 2D UPLC system","lipid profiling assay","Thermo Scientific Q Exactive","Thermo Scientific Q Exactive HF","hyperchylomicronemia","Waters ACQUITY UPC2 System","case control design"],"mass_spectrometry_protocol":["Mass spectrometry was performed using a Thermo Scientific Q Exactive high-resolution mass spectrometer equipped with an electrospray ionization source. Data were acquired in both positive and negative ion modes. The MS scan range was m/z 200–2000. MS1 resolution was 70,000, AGC target was 3e6, and maximum injection time was 100 ms. The top 3 precursor ions were selected for MS2 acquisition. MS2 resolution was 17,500, AGC target was 1e5, and maximum injection time was 50 ms. Stepped normalized collision energies were 15, 30, and 45 eV. ESI parameters were as follows: sheath gas, 40 L/min; auxiliary gas, 10 L/min; spray voltage, 3.80 kV in positive ion mode and 3.20 kV in negative ion mode; capillary temperature, 320°C; auxiliary gas heater temperature, 350°C.
"],"metabolite_name":["FA(22:5)","LPC(20:3)","LPC(20:4)","FA(20:4)","PE(16:0/18:1)","LPC(18:1)","LPC(22:5)"],"additional_accession":[]},"is_claimable":false,"name":"Severe hyperchylomicronemia sensitizes the heart to pathological remodeling: evidence from GPIHBP1 deficient mice","description":"Abstract Aim: Circulating triglyceride and triglyceride-rich lipoprotein (TRL) accumulation is increasingly recognized as a residual atherosclerotic risk, but their specific effect in cardiac remodeling and heart failure (HF) remain largely unexplored. Here we investigated this issue in Gpihbp1 knockout (KO) mice, which develop severe hyperchylomicronemia due to disruption of intravascular TRL hydrolysis . Methods: Cardiac lipid metabolism and remodeling were evaluated in 10-month-old Gpihbp1 KO mice and wild-type littermates under physiological conditions. Mice were also subjected to transverse aortic constriction (TAC) to evaluate the impact of severe hyperchylomicronemia on pressure overload-induced remodeling and HF. Furthermore, Gpihbp1 KO mice were crossed into Ldlr KO background to study hyperchylomicronemia’s effects on hemorheology and high-fat diet (HFD)-induced cardiac pathology. Results: Untargeted cardiac lipidomics revealed 214 differentially regulated lipid species specifically enriched in glycerophospholipids, fatty acid (FA) and diacylglycerol subclasses. qPCR confirmed down-regulated FA oxidation genes and upregulated glucose utilization genes. Electron microscopy showed swollen mitochondria with fragmented cristae, and RNA-seq demonstrated reduced respiratory-chain gene expression. These derangements culminated in impaired cardiac contractile performance in 10-month-old Gpihbp1 KO mice without inducing hypertrophy or fibrosis. After TAC, Gpihbp1 KO hearts exhibited exaggerated diastolic dysfunction, increased myocyte hypertrophy, and fibrosis. In Gpihbp1/Ldlr double knockout (dKO) mice, reduced erythrocyte deformability and increased whole blood viscosity were observed and worsened post-HFD. Additionally, HFD feeding precipitated significant diastolic impairment, cardiac hypertrophy and fibrosis in dKO mice. Conclusion: Severe hyperchylomicronemia due to GPIHBP1 deficiency sensitizes the heart to pathological remodeling and HF. These findings indicate a potential pathogenic contribution of HTG and TRL accumulation to cardiac disease.","dates":{"publication":"2026-06-11","submission":"2026-06-11"},"accession":"MTBLS14749","cross_references":{"KEGG":["C04230","C21484","C13877","C21480","C13861","C00219","C16513"]}}