<HashMap><database>MetaboLights</database><file_versions><headers><Content-Type>application/xml</Content-Type></headers><body><files><Tabular>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/m_MTBLS14881_LC-MS_negative_hilic_v2_maf.tsv</Tabular><Tabular>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/m_MTBLS14881_LC-MS_positive_hilic_v2_maf.tsv</Tabular><Txt>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/i_Investigation.txt</Txt><Txt>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/a_MTBLS14881_LC-MS_negative_hilic.txt</Txt><Txt>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/s_MTBLS14881.txt</Txt><Txt>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881/a_MTBLS14881_LC-MS_positive_hilic.txt</Txt></files><type>primary</type></body><statusCode>OK</statusCode><statusCodeValue>200</statusCodeValue></file_versions><scores/><additional><ftp_download_link>ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14881</ftp_download_link><metabolite_identification_protocol>&lt;p>Lipid features were detected and integrated using BIOTREE BioBud. Lipids were annotated by matching retention time, precursor and product ion m/z, ionization mode, and MS/MS spectra against an in-house library and public databases, including LIPID MAPS, HMDB, and PubChem. Database identifiers, including PubChem CID, HMDB accession, and InChIKey, were assigned according to the matched chemical structures.&lt;/p></metabolite_identification_protocol><repository>MetaboLights</repository><study_status>Public</study_status><ptm_modification></ptm_modification><instrument_platform>Liquid Chromatography MS - positive - hilic</instrument_platform><instrument_platform>Liquid Chromatography MS - negative - hilic</instrument_platform><chromatography_protocol>&lt;p>This project uses an Agilent liquid phase ultra-high performance liquid chromatograph, and the target compounds are separated by liquid phase chromatography columns.&lt;/p>&lt;p>The A phase of the RP liquid phase chromatography is H2O:ACN:MeOH = 1:1:1, v/v/v, containing 7 mmol/L acetic acid ammonium; the B phase is an isopropanol solution, containing 7 mmol/L acetic acid ammonium. The target compounds are separated by the Kinetex C18 (2.1 mm × 100 mm, 2.6 μm, Phenomenex, USA) liquid phase chromatography column. The flow rate of the mobile phase: 0.35 mL/min, column temperature: 45 C, sample plate temperature: 10 C, injection volume: 1 μL.&lt;/p>&lt;p>The HILIC liquid phase chromatography A phase is H2O:ACN = 1:1, v/v, containing 2 mmol/L acetic acid ammonium; the B phase is DCM:ACN = 1:13, v/v, containing 2 mmol/L acetic acid ammonium. The target compounds are separated by the Luna NH2 (Amino) 3μm (2x100 mm, 3 μm, Phenomenex, USA) liquid phase chromatography column. The flow rate of the mobile phase: 0.7 mL/min, column temperature: 40 C, sample plate temperature: 10 C, injection volume: 1 μL.&lt;/p></chromatography_protocol><publication>Macrophage IgG recycling couples glomerular IgG accumulation to podocyte senescence in obesity-related glomerulopathy.</publication><submitter_affiliation>Peking University</submitter_affiliation><submitter_name>Duo Keai</submitter_name><organism_part>kidney</organism_part><technology_type>mass spectrometry assay</technology_type><disease></disease><extraction_protocol>&lt;p>1. Add 250 μL of water to the sample, vortex and mix for 20 seconds, then transfer the sample to a 2 mL EP tube.&lt;/p>&lt;p>2. Freeze-thaw the sample in liquid nitrogen 3 times, and use a cell ultrasonic disintegrator to ultrasonicate for 10 minutes. Take 50 μL of the sample for BCA quantification.&lt;/p>&lt;p>3. Take 200 μL of the sample, add 250 μL of 75% methanol solution, vortex and mix.&lt;/p>&lt;p>4. Add 750 μL of MTBE (with internal standard), vortex and mix for 20 seconds, ultrasonicate for 10 minutes, and let it stand at room temperature for 30 minutes.&lt;/p>&lt;p>5. Add 100 μL of mass spectrometry grade water, vortex and mix for 20 seconds, let it stand at room temperature for 10 minutes.&lt;/p>&lt;p>6. Place the sample at 4°C, centrifuge at 12000 rpm for 15 minutes, and take the supernatant of 650 μL to a new EP tube.&lt;/p>&lt;p>7. Vacuum dry at 25°C.&lt;/p>&lt;p>8. Add 200 μL of the reconstituted solution (DCM:MeOH = 1:1, v/v), vortex and mix for 20 seconds, and ultrasonicate on an ice bath for 10 minutes.&lt;/p>&lt;p>9. Centrifuge the sample at 4°C, 12000 rpm for 15 minutes, and take the supernatant into the injection vial for instrument analysis.&lt;/p></extraction_protocol><organism>Mus musculus</organism><full_dataset_link>https://www.ebi.ac.uk/metabolights/MTBLS14881</full_dataset_link><author>Yangbin Pan. Shanghai Pudong Hospital, Fudan University Pudong Medical Center. panyb2022@126.com.</author><author>Zikang Liu. Shanghai Pudong Hospital, Fudan University Pudong Medical Center. 23111330002@m.fudan.edu.cn.</author><data_transformation_protocol>&lt;p>Vendor-format raw mass spectrometry files were converted to the open mzML format using ProteoWizard MSConvert version. Vendor peak picking was applied to generate centroided spectra. The mzML files were generated with zlib compression and indexed mzML enabled. All acquired MS1 and MS/MS scans were retained, and no additional scan filtering, intensity filtering, or retention-time filtering was applied during conversion. The original vendor-format raw files and the converted mzML files were both deposited in the repository.&lt;/p></data_transformation_protocol><study_factor>Group</study_factor><submitter_email>keaiduoduo998@126.com</submitter_email><sample_collection_protocol>&lt;p>The cell pellets (about 106 cells) or bacteria pellets(about 106 bacteria) were taken, mixed with 200 µL methanol and 750 MTBE (containing internal standard) and were vortexed for 40 s. The sample stands for 30 min at room temperature. Then 200 µL water was added. The sample was vortexed for 20 s and stand for 10 min at room temperature. Then all the samples were centrifuged at 12000 rpm and 4C for 15 min. Transfer 700 μL supernatant of each sample to a 1.5 mL EP tube. 100 μL reconstitution solution (DCM:MeOH=1:1,v/v) was added. Samples were vortexed for 20 sec and sonicated in ice-water bath for 10 min. Then all the samples were centrifuged at 12000 rpm and 4C for 15 min. Transfer supernatant of each sample to glass vial for LC-MS/MS analysis.&lt;/p></sample_collection_protocol><omics_type>Metabolomics</omics_type><study_design>Metabolomics</study_design><study_design>Mus musculus</study_design><study_design>untargeted analysis</study_design><study_design>Obesity-related glomerulopathy</study_design><study_design>IgG</study_design><study_design>Podocyte Senescence</study_design><study_design>Agilent 1290 Infinity LC</study_design><study_design>SMPD3</study_design><study_design>kidney</study_design><study_design>Sphingolipid metabolism</study_design><study_design>podocyte</study_design><study_design>SCIEX Triple QuadTM 7500+</study_design><study_design>Macrophage</study_design><curator_keywords>Metabolomics</curator_keywords><curator_keywords>Mus musculus</curator_keywords><curator_keywords>untargeted analysis</curator_keywords><curator_keywords>Obesity-related glomerulopathy</curator_keywords><curator_keywords>IgG</curator_keywords><curator_keywords>Podocyte Senescence</curator_keywords><curator_keywords>Agilent 1290 Infinity LC</curator_keywords><curator_keywords>SMPD3</curator_keywords><curator_keywords>kidney</curator_keywords><curator_keywords>Sphingolipid metabolism</curator_keywords><curator_keywords>podocyte</curator_keywords><curator_keywords>SCIEX Triple QuadTM 7500+</curator_keywords><curator_keywords>Macrophage</curator_keywords><mass_spectrometry_protocol>&lt;p>During data acquisition, mass spectrometry analysis is performed in the multiple reaction monitoring (MRM) mode. The ion source parameters are as follows: IonSpray Voltage: +3000/-3000 V, Curtain Gas: 35 psi, Temperature: (positive mode 325 C, negative mode 550 C), Ion Source Gas 1: 40 psi, Ion Source Gas 2: 70 psi. The mass spectrometry data acquisition and quantitative analysis of the target compounds are completed through SCIEX OS (3.3.1) and the automated analysis software BIOTREE BioBud (v2.0.4).&lt;/p&gt;</mass_spectrometry_protocol><metabolite_name>CAR(10:1)</metabolite_name><metabolite_name>BMP(14:0_18:2)</metabolite_name><metabolite_name>PS(18:1_22:4)</metabolite_name><metabolite_name>PE(14:0_14:0)</metabolite_name><metabolite_name>PG(16:0_22:4)</metabolite_name><metabolite_name>PA(17:0_20:4)</metabolite_name><metabolite_name>TG(54:3)_FA(20:2)</metabolite_name><metabolite_name>PC(20:3_20:4)</metabolite_name><metabolite_name>TG(52:3)_FA(20:2)</metabolite_name><metabolite_name>TG(56:3)_FA(20:2)</metabolite_name><metabolite_name>PG(16:1_16:1)</metabolite_name><metabolite_name>PE(22:4_22:5)</metabolite_name><metabolite_name>CE(20:5)</metabolite_name><metabolite_name>PA(22:5_22:6)</metabolite_name><metabolite_name>CAR(10:2)</metabolite_name><metabolite_name>PS(18:1_22:5)</metabolite_name><metabolite_name>DG(16:1_16:1)</metabolite_name><metabolite_name>LPE(19:0)</metabolite_name><metabolite_name>PA(17:0_20:3)</metabolite_name><metabolite_name>BMP(16:1_20:0)</metabolite_name><metabolite_name>TG(50:3)_FA(20:3)</metabolite_name><metabolite_name>PC(16:1_22:6)</metabolite_name><metabolite_name>TG(50:0)_FA(14:0)</metabolite_name><metabolite_name>BMP(14:0_18:1)</metabolite_name><metabolite_name>PG(16:0_22:5)</metabolite_name><metabolite_name>TG(54:3)_FA(20:3)</metabolite_name><metabolite_name>PC(20:3_20:3)</metabolite_name><metabolite_name>TG(47:1)_FA(18:1)</metabolite_name><metabolite_name>TG(49:1)_FA(18:1)</metabolite_name><metabolite_name>PC(16:1_22:5)</metabolite_name><metabolite_name>TG(52:3)_FA(20:3)</metabolite_name><metabolite_name>PE(22:4_22:6)</metabolite_name><metabolite_name>PE(P-16:1_18:0)</metabolite_name><metabolite_name>DG(18:3_20:4)</metabolite_name><metabolite_name>PS(18:1_22:2)</metabolite_name><metabolite_name>MGMG(18:2)</metabolite_name><metabolite_name>PA(14:0_20:4)</metabolite_name><metabolite_name>PG(18:3_20:3)</metabolite_name><metabolite_name>BMP(14:0_18:0)</metabolite_name><metabolite_name>DG(20:3_22:5)</metabolite_name><metabolite_name>PE(P-16:1_18:1)</metabolite_name><metabolite_name>TG(45:0)_FA(14:0)</metabolite_name><metabolite_name>PS(18:1_22:3)</metabolite_name><metabolite_name>PE(17:0_22:6)</metabolite_name><metabolite_name>PA(17:0_20:5)</metabolite_name><metabolite_name>FA(18:0)</metabolite_name><metabolite_name>Hex2Cer(d18:1/24:0)</metabolite_name><metabolite_name>TG(47:0)_FA(14:0)</metabolite_name><metabolite_name>PE(P-16:1_18:2)</metabolite_name><metabolite_name>PC(19:0_20:0)</metabolite_name><metabolite_name>PC(20:3_20:5)</metabolite_name><metabolite_name>DG(14:0_15:0)</metabolite_name><metabolite_name>DG(20:3_22:6)</metabolite_name><metabolite_name>PC(16:0_19:0)</metabolite_name><metabolite_name>PA(16:0_18:2)</metabolite_name><metabolite_name>PA(14:0_20:2)</metabolite_name><metabolite_name>PE(P-20:1_15:0)</metabolite_name><metabolite_name>PS(18:0_20:1)</metabolite_name><metabolite_name>PA(17:0_20:0)</metabolite_name><metabolite_name>TG(58:10)_FA(20:5)</metabolite_name><metabolite_name>Hex2Cer(d18:1/24:1)</metabolite_name><metabolite_name>FA(18:1)</metabolite_name><metabolite_name>DG(19:0_22:5)</metabolite_name><metabolite_name>BMP(16:1_20:3)</metabolite_name><metabolite_name>DG(18:3_20:1)</metabolite_name><metabolite_name>PE(P-16:1_18:3)</metabolite_name><metabolite_name>PA(14:0_20:1)</metabolite_name><metabolite_name>PS(18:0_20:0)</metabolite_name><metabolite_name>FA(18:2)</metabolite_name><metabolite_name>DG(18:3_20:0)</metabolite_name><metabolite_name>PE(P-18:0_18:1)</metabolite_name><metabolite_name>PE(14:0_22:6)</metabolite_name><metabolite_name>MGDG(16:3_20:3)</metabolite_name><metabolite_name>DG(20:3_22:4)</metabolite_name><metabolite_name>LPC(18:2)</metabolite_name><metabolite_name>DG(16:0_22:6)</metabolite_name><metabolite_name>PA(16:0_18:0)</metabolite_name><metabolite_name>HexCer(d18:1/20:1)</metabolite_name><metabolite_name>PS(18:1_22:6)</metabolite_name><metabolite_name>PA(14:0_20:0)</metabolite_name><metabolite_name>PA(17:0_20:2)</metabolite_name><metabolite_name>FA(18:3)</metabolite_name><metabolite_name>BMP(16:1_20:1)</metabolite_name><metabolite_name>PC(16:1_22:4)</metabolite_name><metabolite_name>LPC(18:1)</metabolite_name><metabolite_name>LPG(16:0)</metabolite_name><metabolite_name>DG(16:0_22:5)</metabolite_name><metabolite_name>DG(16:0_22:4)</metabolite_name><metabolite_name>PA(16:0_18:1)</metabolite_name><metabolite_name>HexCer(d18:1/20:0)</metabolite_name><metabolite_name>PA(17:0_20:1)</metabolite_name><metabolite_name>DG(19:0_22:6)</metabolite_name><metabolite_name>BMP(16:1_20:2)</metabolite_name><metabolite_name>LPC(18:0)</metabolite_name><metabolite_name>CE(24:0)</metabolite_name><metabolite_name>PE(P-18:0_18:3)</metabolite_name><metabolite_name>LPG(16:1)</metabolite_name><metabolite_name>PE(20:5_22:5)</metabolite_name><metabolite_name>TG(44:1)_FA(16:0)</metabolite_name><metabolite_name>PE(P-20:1_19:0)</metabolite_name><metabolite_name>PE(15:0_20:2)</metabolite_name><metabolite_name>CL(72:6)_FA(18:0)</metabolite_name><metabolite_name>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te_name>PE(14:0_22:4)</metabolite_name><metabolite_name>PA(18:2_20:1)</metabolite_name><metabolite_name>PA(18:0_20:3)</metabolite_name><metabolite_name>TG(52:5)_FA(22:5)</metabolite_name><metabolite_name>PE(O-18:0_22:5)</metabolite_name><metabolite_name>TG(58:9)_FA(18:2)</metabolite_name><metabolite_name>PE(P-16:1_16:0)</metabolite_name><metabolite_name>FA(20:5)</metabolite_name><metabolite_name>PC(14:0_16:1)</metabolite_name><metabolite_name>PE(20:0_20:5)</metabolite_name><metabolite_name>TG(53:3)_FA(16:0)</metabolite_name><metabolite_name>PA(18:1_19:0)</metabolite_name><metabolite_name>PS(16:0_18:0)</metabolite_name><metabolite_name>PE(18:0_18:1)</metabolite_name><metabolite_name>PE(22:5_22:6)</metabolite_name><metabolite_name>TG(49:0)_FA(17:0)</metabolite_name><metabolite_name>PA(18:0_20:2)</metabolite_name><metabolite_name>PE(O-18:0_22:6)</metabolite_name><metabolite_name>PE(20:1_20:3)</metabolite_name><metabolite_name>PE(P-16:1_16:1)</metabolite_name><metabolite_name>PC(14:0_16:0)</metabolite_name><metabolite_name>FA(20:4)</metabolite_name><metabolite_name>PE(18:2_18:2)</metabolite_name><metabolite_name>PA(15:0_22:5)</metabolite_name><metabolite_name>BMP(16:0_18:1)</metabolite_name><metabolite_name>CAR(2:0)</metabolite_name><metabolite_name>TG(53:4)_FA(18:3)</metabolite_name><metabolite_name>TG(53:4)_FA(18:2)</metabolite_name><metabolite_name>PS(16:0_18:1)</metabolite_name><metabolite_name>PA(18:1_20:0)</metabolite_name><metabolite_name>PE(18:0_18:0)</metabolite_name><metabolite_name>TG(56:2)_FA(18:0)</metabolite_name><metabolite_name>PE(22:5_22:5)</metabolite_name><metabolite_name>PA(15:0_22:6)</metabolite_name><metabolite_name>PA(18:0_20:1)</metabolite_name><metabolite_name>PE(20:1_20:4)</metabolite_name><metabolite_name>BMP(16:1_18:0)</metabolite_name><metabolite_name>PE(20:0_20:3)</metabolite_name><metabolite_name>PE(O-16:0_20:5)</metabolite_name><metabolite_name>PC(15:0_19:0)</metabolite_name><metabolite_name>BMP(16:0_18:0)</metabolite_name><metabolite_name>TG(58:7)_FA(18:1)</metabolite_name><metabolite_name>TG(47:1)_FA(14:0)</metabolite_name><metabolite_name>TG(50:5)_FA(16:0)</metabolite_name><metabolite_name>BMP(20:4_22:0)</metabolite_name><metabolite_name>PE(18:0_18:3)</metabolite_name><metabolite_name>PE(20:2_20:2)</metabolite_name><metabolite_name>PE(20:1_20:1)</metabolite_name><metabolite_name>TG(42:1)_FA(16:1)</metabolite_name><metabolite_name>TG(52:7)_FA(22:6)</metabolite_name><metabolite_name>TG(58:7)_FA(18:0)</metabolite_name><metabolite_name>PE(20:0_20:4)</metabolite_name><metabolite_name>PE(O-16:0_20:4)</metabolite_name><metabolite_name>PE(18:1_18:1)</metabolite_name><metabolite_name>PE(18:0_18:2)</metabolite_name><metabolite_name>PE(20:1_20:2)</metabolite_name><metabolite_name>TG(52:4)_FA(20:4)</metabolite_name><metabolite_name>PE(22:4_22:4)</metabolite_name></additional><is_claimable>false</is_claimable><name>Macrophage IgG recycling couples glomerular IgG accumulation to podocyte senescence in obesity-related glomerulopathy</name><description>Background: Obesity-related glomerulopathy (ORG) is increasingly common, yet its pathogenesis remains poorly understood. This study aimed to elucidate the mechanisms by which nonspecific glomerular IgG deposition promotes podocyte senescence in ORG, thereby expanding potential therapeutic options. Methods: ORG patient samples and diet-induced obese (DIO) mice were used to compare glomerular IgG localization and abundance in obese versus control states. Causality between glomerular IgG accumulation and podocyte senescence was assessed by exogenous IgG supplementation and B cell deficiency. Primary podocytes were IgG-stimulated for transcriptomic and lipidomic profiling, and SMPD3 was validated by in vitro and in vivo loss-of-function studies. Macrophage-specific FcRn deletion and anti-CD20 therapy were further used to evaluate IgG-targeted strategies for mitigating podocyte senescence and injury in ORG. Results: In ORG patient kidneys and DIO mice, glomerular IgG deposition was markedly increased. Exogenous IgG supplementation in non-obese mice reproduced the glomerular IgG accumulation and podocyte senescence observed in HFD fed mice. Conversely, B null DIO mice and anti-CD20 treated DIO mice showed greatly reduced glomerular IgG levels and attenuated podocyte injury. Mechanistically, IgG exposure activated podocyte sphingolipid metabolism, notably upregulating Smpd3 and increasing intra-podocyte ceramide. In vitro and in vivo Smpd3 knockdown prevented IgG induced ceramide accumulation and podocyte senescence. Obesity also heightened glomerular macrophage infiltration, and macrophage depletion or macrophage-specific FcRn knockout significantly reduced glomerular IgG deposition and protected against podocyte injury and senescence. Conclusions: FcRn-expressing macrophages mediate obesity-induced IgG retention in glomeruli, which drives podocyte ceramide overload and 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