#METABOLOMICS WORKBENCH mlhomme_20221213_043543 DATATRACK_ID:3642 STUDY_ID:ST002400 ANALYSIS_ID:AN003908 VERSION 1 CREATED_ON 12-16-2022 #PROJECT PR:PROJECT_TITLE Alcohol dehydrogenase 1B is crucial for adipocyte homeostasis. PR:PROJECT_SUMMARY Background. Alcohol dehydrogenase (ADH1B), encoded by the ADH1B gene, is a PR:PROJECT_SUMMARY cytosolic enzyme mainly known for its role in ethanol catabolism in the liver. A PR:PROJECT_SUMMARY few studies have paved the way to show an equally important role of ADH1B in PR:PROJECT_SUMMARY adipocytes. This study aimed to better identify the cellular mechanisms and PR:PROJECT_SUMMARY signaling pathways involving ADH1B in adipose tissue and to determine if ADH1B PR:PROJECT_SUMMARY variants might contribute to adipose tissue dysfunction. Results. We showed that PR:PROJECT_SUMMARY CRISPR-Cas9-mediated ADH1B knockout (KO) in human adipose stem cells (ASC) PR:PROJECT_SUMMARY abolished adipocyte differentiation and decreased insulin response. This was PR:PROJECT_SUMMARY accompanied by oxidative stress, altered mitochondrial functions, and cellular PR:PROJECT_SUMMARY senescence. Lipidomic analysis revealed that ADH1B deficiency results in a major PR:PROJECT_SUMMARY remodeling of lipid composition in ASC. An ADH1B homozygous loss-of-function PR:PROJECT_SUMMARY variant was also identified in a patient presenting with a lipodystrophic and PR:PROJECT_SUMMARY insulin resistant syndrome associated with major liver dysfunction, leading to PR:PROJECT_SUMMARY early death. Discussion. This translational study underlines the crucial role of PR:PROJECT_SUMMARY ADH1B in adipose tissue. It unveils cellular mechanisms accounting for its key PR:PROJECT_SUMMARY role in adipogenesis, and adipocyte homeostasis. This study also identifies PR:PROJECT_SUMMARY ADH1B as a candidate gene in monogenic forms of lipodystrophic and insulin PR:PROJECT_SUMMARY resistant syndromes. PR:INSTITUTE INSERM PR:LAST_NAME Gautheron PR:FIRST_NAME Jérémie PR:ADDRESS 27 rue Chaligny, 75012 Paris France PR:EMAIL jeremie.gautheron@gmail.com PR:PHONE +33623398373 PR:DOI http://dx.doi.org/10.21228/M8VM64 #STUDY ST:STUDY_TITLE Alcohol dehydrogenase 1B is crucial for adipocyte homeostasis ST:STUDY_SUMMARY Background. Alcohol dehydrogenase (ADH1B), encoded by the ADH1B gene, is a ST:STUDY_SUMMARY cytosolic enzyme mainly known for its role in ethanol catabolism in the liver. A ST:STUDY_SUMMARY few studies have paved the way to show an equally important role of ADH1B in ST:STUDY_SUMMARY adipocytes. This study aimed to better identify the cellular mechanisms and ST:STUDY_SUMMARY signaling pathways involving ADH1B in adipose tissue and to determine if ADH1B ST:STUDY_SUMMARY variants might contribute to adipose tissue dysfunction. Results. We showed that ST:STUDY_SUMMARY CRISPR-Cas9-mediated ADH1B knockout (KO) in human adipose stem cells (ASC) ST:STUDY_SUMMARY abolished adipocyte differentiation and decreased insulin response. This was ST:STUDY_SUMMARY accompanied by oxidative stress, altered mitochondrial functions, and cellular ST:STUDY_SUMMARY senescence. Lipidomic analysis revealed that ADH1B deficiency results in a major ST:STUDY_SUMMARY remodeling of lipid composition in ASC. An ADH1B homozygous loss-of-function ST:STUDY_SUMMARY variant was also identified in a patient presenting with a lipodystrophic and ST:STUDY_SUMMARY insulin resistant syndrome associated with major liver dysfunction, leading to ST:STUDY_SUMMARY early death. Discussion. This translational study underlines the crucial role of ST:STUDY_SUMMARY ADH1B in adipose tissue. It unveils cellular mechanisms accounting for its key ST:STUDY_SUMMARY role in adipogenesis, and adipocyte homeostasis. This study also identifies ST:STUDY_SUMMARY ADH1B as a candidate gene in monogenic forms of lipodystrophic and insulin ST:STUDY_SUMMARY resistant syndromes. ST:INSTITUTE INSERM ST:LAST_NAME Gautheron ST:FIRST_NAME Jérémie ST:ADDRESS 27 rue Chaligny ST:EMAIL jeremie.gautheron@gmail.com ST:PHONE +33623398373 ST:SUBMIT_DATE 2022-12-13 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS ADH1B_KO_01_LIP329 ADH1B_KO_01_LIP329 Genotype:ADH1B_KO Batch=1; RAW_FILE_NAME=LIP329_C18_1x_KO_01; RAW_FILE_NAME=LIP329_C18_10x_KO_01; RAW_FILE_NAME=LIP329_long_1x_KO_01; RAW_FILE_NAME=LIP329_short_1x_KO_01; RAW_FILE_NAME=LIP329_short_20x_KO_01 SUBJECT_SAMPLE_FACTORS ADH1B_KO_02_LIP329 ADH1B_KO_02_LIP329 Genotype:ADH1B_KO Batch=1; RAW_FILE_NAME=LIP329_C18_1x_KO_02; RAW_FILE_NAME=LIP329_C18_10x_KO_02; RAW_FILE_NAME=LIP329_long_1x_KO_02; RAW_FILE_NAME=LIP329_short_1x_KO_02; RAW_FILE_NAME=LIP329_short_20x_KO_02 SUBJECT_SAMPLE_FACTORS ADH1B_KO_03_LIP329 ADH1B_KO_03_LIP329 Genotype:ADH1B_KO Batch=1; RAW_FILE_NAME=LIP329_C18_1x_KO_03; RAW_FILE_NAME=LIP329_C18_10x_KO_03; RAW_FILE_NAME=LIP329_long_1x_KO_03; RAW_FILE_NAME=LIP329_short_1x_KO_03; RAW_FILE_NAME=LIP329_short_20x_KO_03 SUBJECT_SAMPLE_FACTORS ADH1B_KO_04_LIP329 ADH1B_KO_04_LIP329 Genotype:ADH1B_KO Batch=1; RAW_FILE_NAME=LIP329_C18_1x_KO_04; RAW_FILE_NAME=LIP329_C18_10x_KO_04; RAW_FILE_NAME=LIP329_long_1x_KO_04; RAW_FILE_NAME=LIP329_short_1x_KO_04; RAW_FILE_NAME=LIP329_short_20x_KO_04 SUBJECT_SAMPLE_FACTORS ADH1B_KO_05_LIP329 ADH1B_KO_05_LIP329 Genotype:ADH1B_KO Batch=1; RAW_FILE_NAME=LIP329_C18_1x_KO_05; RAW_FILE_NAME=LIP329_C18_10x_KO_05; RAW_FILE_NAME=LIP329_long_1x_KO_05; RAW_FILE_NAME=LIP329_short_1x_KO_05; RAW_FILE_NAME=LIP329_short_20x_KO_05 SUBJECT_SAMPLE_FACTORS CTL_01_LIP329 CTL_01_LIP329 Genotype:CTL Batch=1; RAW_FILE_NAME=LIP329_C18_1x_CTL_01; RAW_FILE_NAME=LIP329_C18_10x_CTL_01; RAW_FILE_NAME=LIP329_long_1x_CTL_01; RAW_FILE_NAME=LIP329_short_1x_CTL_01; RAW_FILE_NAME=LIP329_short_20x_CTL_01 SUBJECT_SAMPLE_FACTORS CTL_02_LIP329 CTL_02_LIP329 Genotype:CTL Batch=1; RAW_FILE_NAME=LIP329_C18_1x_CTL_02; RAW_FILE_NAME=LIP329_C18_10x_CTL_02; RAW_FILE_NAME=LIP329_long_1x_CTL_02; RAW_FILE_NAME=LIP329_short_1x_CTL_02; RAW_FILE_NAME=LIP329_short_20x_CTL_02 SUBJECT_SAMPLE_FACTORS CTL_03_LIP329 CTL_03_LIP329 Genotype:CTL Batch=1; RAW_FILE_NAME=LIP329_C18_1x_CTL_03; RAW_FILE_NAME=LIP329_C18_10x_CTL_03; RAW_FILE_NAME=LIP329_long_1x_CTL_03; RAW_FILE_NAME=LIP329_short_1x_CTL_03; RAW_FILE_NAME=LIP329_short_20x_CTL_03 SUBJECT_SAMPLE_FACTORS CTL_04_LIP329 CTL_04_LIP329 Genotype:CTL Batch=1; RAW_FILE_NAME=LIP329_C18_1x_CTL_04; RAW_FILE_NAME=LIP329_C18_10x_CTL_04; RAW_FILE_NAME=LIP329_long_1x_CTL_04; RAW_FILE_NAME=LIP329_short_1x_CTL_04; RAW_FILE_NAME=LIP329_short_20x_CTL_04 SUBJECT_SAMPLE_FACTORS CTL_05_LIP329 CTL_05_LIP329 Genotype:CTL Batch=1; RAW_FILE_NAME=LIP329_C18_1x_CTL_05; RAW_FILE_NAME=LIP329_C18_10x_CTL_05; RAW_FILE_NAME=LIP329_long_1x_CTL_05; RAW_FILE_NAME=LIP329_short_1x_CTL_05; RAW_FILE_NAME=LIP329_short_20x_CTL_05 #COLLECTION CO:COLLECTION_SUMMARY ASC were isolated from surgical samples of subcutaneous abdominal adipose tissue CO:COLLECTION_SUMMARY from a 25-year-old healthy woman with a normal body mass index (BMI). Adipose CO:COLLECTION_SUMMARY tissue was enzymatically digested with collagenase B (0.2%). CO:SAMPLE_TYPE Adipose tissue #TREATMENT TR:TREATMENT_SUMMARY After centrifugation, stromal vascular fraction was filtered, rinsed, plated and TR:TREATMENT_SUMMARY cultured in α-MEM with 10% Fetal Calf Serum (FCS), 1% GlutaMAX (#35050061, TR:TREATMENT_SUMMARY Thermo Fisher Scientific), 1% Penicillin/streptomycin (PS - 10,000 UI/mL), 1% TR:TREATMENT_SUMMARY HEPES and Fibroblast Growth Factor-2 (FGF-2 -145 nmol/L). After 24 h, only ASC TR:TREATMENT_SUMMARY adhered to plastic surfaces, while other cells were removed after culture medium TR:TREATMENT_SUMMARY replacement. ASC were maintained in an undifferentiated state in α-MEM TR:TREATMENT_SUMMARY supplemented with 10 % newborn calf serum (#CA-1151500; Biosera, MI, USA), 1% TR:TREATMENT_SUMMARY GlutaMAX, HEPES and P/S, and FGF-2 (145 nmol/L). Adipocyte differentiation was TR:TREATMENT_SUMMARY induced by treating 2-day post-confluent cultures with high-glucose (25 mmol/L) TR:TREATMENT_SUMMARY DMEM supplemented with 10 % FCS, 1 % PS, 1 µmol/L dexamethasone (#D4902; TR:TREATMENT_SUMMARY Sigma-Aldrich, MI, USA), 1 µM rosiglitazone (#D4902; Sigma-Aldrich), 250 µM TR:TREATMENT_SUMMARY 3-isobutyl-1-methyl xanthine (IBMX) (#I7018; Sigma-Aldrich) and 0.17 µmol/L TR:TREATMENT_SUMMARY insulin (#I0516; Sigma-Aldrich) for ten days. The medium was then replaced with TR:TREATMENT_SUMMARY high-glucose DMEM supplemented with 10% FCS, 1 % PS, 1 µmol/L rosiglitazone and TR:TREATMENT_SUMMARY 0.17 µM insulin, and changed to fresh medium every 2 days until the 20th day. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Lipid extraction. Lipids were extracted from ASC cells according to a modified SP:SAMPLEPREP_SUMMARY Folch method. Cell pellets were resuspended in 100µl methanol and supplemented SP:SAMPLEPREP_SUMMARY with deuterated internal standards. Lipids were extracted with 1.5 mL chloroform SP:SAMPLEPREP_SUMMARY and 650 µL methanol, sonicated for 15 min. Phase separation was triggered by SP:SAMPLEPREP_SUMMARY addition of 450 µL of ammonium carbonate (250 mM). Lower organic phase was SP:SAMPLEPREP_SUMMARY dried and resuspended in 200 µL of liquid chromatography – mass spectrometry SP:SAMPLEPREP_SUMMARY (LC-MS) solvent. #CHROMATOGRAPHY CH:INSTRUMENT_NAME Shimadzu 20AD CH:COLUMN_NAME Phenomenex Kinetex HILIC (150 x 3mm,2.6um) CH:COLUMN_TEMPERATURE 45 CH:FLOW_GRADIENT - CH:FLOW_RATE 300ul/min CH:SOLVENT_A 100% water; 0.2% acetic acid; 30mM ammonium acetate CH:SOLVENT_B 100% acetonitrile; 0.2% acetic acid CH:CHROMATOGRAPHY_TYPE HILIC #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 4000 QTrap MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE ESI MS:MS_COMMENTS MRM acquisition of narrow chromatographic peaks of low abundant phospho- and MS:MS_COMMENTS sphingolipid classes: cer, PG, PI, PE, PE-P This acquisition is referred to as MS:MS_COMMENTS "short_1x" MS:ION_MODE POSITIVE #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS mol% of total lipids MS_METABOLITE_DATA_START Samples ADH1B_KO_01_LIP329 ADH1B_KO_02_LIP329 ADH1B_KO_03_LIP329 ADH1B_KO_04_LIP329 ADH1B_KO_05_LIP329 CTL_01_LIP329 CTL_02_LIP329 CTL_03_LIP329 CTL_04_LIP329 CTL_05_LIP329 Factors Genotype:ADH1B_KO Genotype:ADH1B_KO Genotype:ADH1B_KO Genotype:ADH1B_KO Genotype:ADH1B_KO Genotype:CTL Genotype:CTL Genotype:CTL Genotype:CTL Genotype:CTL Cer(d18:0/14:0) 0.0007 0.0010 0.0011 0.0008 0.0010 Cer(d18:0/16:0) 0.0094 0.0082 0.0116 0.0123 0.0141 0.0233 0.0261 0.0226 0.0262 0.0260 Cer(d18:0/18:0) 0.0016 0.0018 0.0024 0.0015 0.0018 0.0028 0.0030 0.0030 0.0033 0.0029 Cer(d18:0/18:1) 0.0019 0.0011 0.0011 0.0009 0.0011 0.0011 0.0010 Cer(d18:0/20:0) 0.0025 0.0017 0.0026 0.0030 0.0045 0.0037 0.0036 0.0030 Cer(d18:0/22:0) 0.0032 0.0034 0.0044 0.0042 0.0056 0.0089 0.0091 0.0073 0.0072 0.0067 Cer(d18:0/23:0) 0.0007 0.0012 0.0013 0.0012 0.0011 0.0018 0.0014 0.0015 Cer(d18:0/24:0) 0.0027 0.0019 0.0037 0.0028 0.0042 0.0067 0.0056 0.0052 0.0059 0.0045 Cer(d18:0/24:1) 0.0038 0.0037 0.0041 0.0062 0.0056 0.0115 0.0132 0.0124 0.0135 0.0135 Cer(d18:0/24:2) 0.0003 0.0003 0.0005 0.0004 0.0005 0.0011 0.0010 0.0011 0.0009 0.0011 Cer(d18:0/24:3) 0.0002 0.0003 0.0003 0.0002 0.0004 0.0004 0.0006 0.0005 0.0006 0.0005 Cer(d18:0/25:0) 0.0001 0.0001 0.0001 0.0000 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 Cer(d18:0/25:1) 0.0017 0.0022 0.0020 0.0018 0.0022 0.0050 0.0048 0.0054 0.0044 0.0048 Cer(d18:0/25:2) 0.0012 0.0020 0.0014 0.0015 0.0017 0.0036 0.0037 0.0047 0.0038 0.0043 Cer(d18:0/26:0) 0.0000 0.0001 0.0000 0.0000 0.0001 0.0000 0.0000 0.0001 0.0001 0.0000 Cer(d18:0/26:1) 0.0000 0.0003 0.0002 0.0001 0.0001 0.0002 0.0001 0.0002 0.0002 0.0002 Cer(d18:0/26:2) 0.0001 0.0001 0.0001 0.0002 0.0003 0.0003 0.0003 0.0002 Cer(d18:1/14:0) 0.0024 0.0020 0.0020 0.0024 0.0022 0.0041 0.0040 0.0043 0.0042 0.0049 Cer(d18:1/16:0) 0.0955 0.0877 0.0905 0.0857 0.1053 0.1029 0.1056 0.1146 0.1058 0.1142 Cer(d18:1/18:0) 0.0208 0.0198 0.0224 0.0204 0.0283 0.0215 0.0233 0.0235 0.0232 0.0259 Cer(d18:1/18:1) 0.0006 0.0007 0.0006 0.0007 0.0007 0.0007 0.0007 0.0008 0.0008 0.0008 Cer(d18:1/20:0) 0.0042 0.0039 0.0048 0.0042 0.0061 0.0087 0.0087 0.0100 0.0092 0.0102 Cer(d18:1/22:0) 0.0306 0.0313 0.0351 0.0316 0.0468 0.0560 0.0565 0.0601 0.0579 0.0635 Cer(d18:1/23:0) 0.0100 0.0099 0.0116 0.0102 0.0149 0.0181 0.0182 0.0177 0.0176 0.0180 Cer(d18:1/24:0) 0.0618 0.0616 0.0702 0.0646 0.0969 0.1172 0.1136 0.1109 0.1104 0.1181 Cer(d18:1/24:1) 0.0519 0.0526 0.0598 0.0580 0.0777 0.1136 0.1155 0.1114 0.1087 0.1148 Cer(d18:1/24:2) 0.0041 0.0039 0.0047 0.0046 0.0054 0.0108 0.0109 0.0098 0.0098 0.0120 Cer(d18:1/24:3) 0.0010 0.0011 0.0011 0.0010 0.0013 0.0025 0.0027 0.0022 0.0023 0.0023 Cer(d18:1/25:0) 0.0017 0.0016 0.0020 0.0020 0.0025 0.0038 0.0035 0.0033 0.0035 0.0039 Cer(d18:1/25:1) 0.0011 0.0010 0.0013 0.0013 0.0016 0.0034 0.0031 0.0030 0.0032 0.0035 Cer(d18:1/25:2) 0.0003 0.0003 0.0004 0.0004 0.0004 0.0008 0.0008 0.0007 0.0008 0.0009 Cer(d18:1/26:0) 0.0006 0.0007 0.0007 0.0007 0.0008 0.0017 0.0014 0.0015 0.0015 0.0015 Cer(d18:1/26:1) 0.0011 0.0010 0.0012 0.0012 0.0016 0.0044 0.0043 0.0035 0.0041 0.0045 Cer(d18:1/26:2) 0.0002 0.0002 0.0003 0.0003 0.0004 0.0011 0.0012 0.0010 0.0011 0.0013 Cer(d18:2/14:0) 0.0003 0.0003 0.0003 0.0003 0.0004 0.0004 0.0004 0.0004 0.0004 Cer(d18:2/16:0) 0.0165 0.0159 0.0148 0.0178 0.0142 0.0127 0.0117 0.0126 0.0131 0.0146 Cer(d18:2/18:0) 0.0104 0.0111 0.0106 0.0118 0.0102 0.0068 0.0063 0.0078 0.0077 0.0084 Cer(d18:2/18:1) 0.0002 0.0002 0.0002 0.0002 0.0002 Cer(d18:2/20:0) 0.0016 0.0019 0.0016 0.0017 0.0018 0.0018 0.0017 0.0020 0.0019 0.0020 Cer(d18:2/21:0) 0.0003 0.0004 0.0004 0.0003 0.0004 0.0003 0.0003 0.0004 0.0003 0.0004 Cer(d18:2/22:0) 0.0120 0.0140 0.0138 0.0146 0.0142 0.0125 0.0125 0.0129 0.0133 0.0145 Cer(d18:2/23:0) 0.0035 0.0041 0.0043 0.0045 0.0045 0.0033 0.0034 0.0035 0.0036 0.0039 Cer(d18:2/23:1) 0.0013 0.0016 0.0013 0.0017 0.0015 0.0016 0.0016 0.0017 0.0017 0.0019 Cer(d18:2/24:0) 0.0252 0.0286 0.0306 0.0310 0.0347 0.0260 0.0233 0.0213 0.0236 0.0254 Cer(d18:2/24:1) 0.0212 0.0236 0.0248 0.0265 0.0250 0.0300 0.0277 0.0254 0.0272 0.0289 Cer(d18:2/24:2) 0.0015 0.0017 0.0017 0.0019 0.0020 0.0023 0.0021 0.0018 0.0020 0.0021 Cer(d18:2/24:3) 0.0004 0.0004 0.0004 0.0004 0.0004 0.0006 0.0004 0.0004 0.0005 0.0005 Cer(d18:2/25:0) 0.0007 0.0008 0.0009 0.0008 0.0010 0.0009 0.0008 0.0007 0.0008 0.0008 Cer(d18:2/25:1) 0.0007 0.0007 0.0008 0.0008 0.0008 0.0010 0.0009 0.0009 0.0009 0.0010 Cer(d18:2/25:2) 0.0002 0.0001 0.0002 0.0002 0.0002 0.0002 0.0002 0.0002 0.0002 0.0002 Cer(d18:2/26:0) 0.0003 0.0005 0.0005 0.0005 0.0006 0.0005 0.0005 0.0005 0.0005 0.0005 Cer(d18:2/26:1) 0.0005 0.0006 0.0006 0.0007 0.0007 0.0010 0.0011 0.0009 0.0009 0.0011 Cer(d18:2/26:2) 0.0001 0.0002 0.0001 0.0002 0.0002 0.0003 0.0003 0.0003 0.0003 0.0003 hex2Cer(d18:0/14:0) 0.0008 0.0008 0.0008 0.0007 0.0009 0.0009 0.0010 0.0009 0.0009 0.0008 hex2Cer(d18:0/16:0) 0.0007 0.0006 0.0010 0.0015 0.0008 0.0014 0.0013 0.0012 0.0013 0.0017 hex2Cer(d18:0/18:0) 0.0002 0.0003 0.0002 0.0003 0.0004 0.0003 0.0003 0.0004 0.0002 0.0005 hex2Cer(d18:0/22:0) 0.0006 0.0005 0.0010 0.0009 0.0010 0.0008 0.0013 hex2Cer(d18:1/14:0) 0.0001 0.0001 0.0001 0.0002 0.0001 0.0002 0.0001 0.0002 0.0002 0.0003 hex2Cer(d18:1/16:0) 0.0036 0.0027 0.0035 0.0069 0.0043 0.0063 0.0048 0.0048 0.0046 0.0072 hex2Cer(d18:1/18:0) 0.0008 0.0005 0.0008 0.0013 0.0009 0.0009 0.0008 0.0009 0.0008 0.0012 hex2Cer(d18:1/20:0) 0.0001 0.0001 0.0001 0.0002 0.0002 0.0004 0.0003 0.0003 0.0003 0.0005 hex2Cer(d18:1/22:0) 0.0008 0.0007 0.0009 0.0016 0.0012 0.0022 0.0018 0.0020 0.0017 0.0028 hex2Cer(d18:1/23:0) 0.0002 0.0001 0.0002 0.0003 0.0003 0.0004 0.0004 0.0003 0.0003 0.0005 hex2Cer(d18:1/24:0) 0.0011 0.0008 0.0013 0.0021 0.0015 0.0034 0.0025 0.0027 0.0024 0.0039 hex2Cer(d18:1/24:1) 0.0008 0.0006 0.0008 0.0015 0.0011 0.0027 0.0021 0.0022 0.0020 0.0034 hex2Cer(d18:1/24:2) 0.0001 0.0001 0.0001 0.0002 0.0002 0.0004 0.0003 0.0004 0.0003 0.0005 hex2Cer(d18:1/25:0) 0.0000 0.0000 0.0000 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0002 hex2Cer(d18:1/25:1) 0.0000 0.0000 0.0000 0.0001 0.0000 0.0001 0.0001 0.0001 0.0001 0.0002 hex2Cer(d18:1/25:2) 0.0000 0.0000 0.0000 0.0001 0.0001 0.0002 0.0001 0.0002 0.0001 0.0002 hex2Cer(d18:1/26:0) 0.0001 0.0001 0.0001 0.0002 0.0001 0.0003 0.0003 0.0003 0.0002 0.0004 hex2Cer(d18:1/26:1) 0.0000 0.0000 0.0000 0.0002 0.0001 0.0001 0.0001 0.0002 hex2Cer(d18:1/26:2) 0.0000 0.0000 0.0001 0.0000 0.0000 0.0000 0.0001 hex2Cer(d18:2/16:0) 0.0001 0.0001 0.0002 0.0002 0.0002 0.0002 0.0002 0.0002 0.0001 0.0002 hex2Cer(d18:2/18:0) 0.0002 0.0000 0.0002 0.0002 0.0002 0.0002 0.0001 0.0002 0.0001 0.0002 hex2Cer(d18:2/20:0) 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 hex2Cer(d18:2/22:0) 0.0001 0.0001 0.0001 0.0002 0.0001 0.0001 0.0001 0.0001 0.0001 0.0002 hex2Cer(d18:2/23:0) 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 hex2Cer(d18:2/23:1) 0.0000 0.0000 0.0000 0.0000 0.0000 0.0000 hexCer(d16:1/20:0) 0.0002 0.0003 0.0003 0.0004 0.0003 0.0003 0.0002 0.0003 0.0003 0.0003 hexCer(d16:1/22:0) 0.0011 0.0010 0.0012 0.0017 0.0014 0.0009 0.0006 0.0006 0.0007 0.0008 hexCer(d18:0/14:0) 0.0001 0.0002 0.0003 0.0002 0.0001 0.0003 0.0002 0.0002 0.0003 0.0002 hexCer(d18:0/16:0) 0.0104 0.0085 0.0105 0.0152 0.0097 0.0093 0.0080 0.0070 0.0075 0.0089 hexCer(d18:0/18:0) 0.0017 0.0014 0.0021 0.0019 0.0019 0.0019 0.0018 0.0015 0.0014 0.0019 hexCer(d18:0/18:1) 0.0012 0.0010 0.0013 0.0018 0.0014 0.0006 0.0006 0.0005 0.0005 0.0006 hexCer(d18:0/20:0) 0.0014 0.0008 0.0013 0.0015 0.0016 0.0031 0.0023 0.0020 0.0027 0.0031 hexCer(d18:0/22:0) 0.0053 0.0034 0.0061 0.0079 0.0075 0.0060 0.0057 0.0053 0.0049 0.0071 hexCer(d18:0/24:0) 0.0025 0.0027 0.0024 0.0039 0.0038 0.0027 0.0022 0.0030 0.0021 0.0029 hexCer(d18:0/24:1) 0.0071 0.0060 0.0083 0.0099 0.0109 0.0089 0.0071 0.0090 0.0078 0.0095 hexCer(d18:0/24:2) 0.0057 0.0058 0.0066 0.0081 0.0078 0.0073 0.0059 0.0074 0.0061 0.0077 hexCer(d18:0/25:0) 0.0002 0.0002 0.0001 0.0003 0.0002 0.0002 0.0002 0.0002 0.0002 0.0002 hexCer(d18:0/25:1) 0.0014 0.0014 0.0016 0.0021 0.0023 0.0022 0.0017 0.0022 0.0016 0.0021 hexCer(d18:0/25:2) 0.0011 0.0012 0.0014 0.0017 0.0015 0.0021 0.0016 0.0020 0.0017 0.0021 hexCer(d18:0/26:1) 0.0001 0.0002 0.0001 0.0002 0.0002 0.0001 0.0001 0.0002 hexCer(d18:0/26:2) 0.0002 0.0003 0.0004 0.0004 0.0004 0.0003 0.0005 hexCer(d18:1/14:0) 0.0015 0.0014 0.0014 0.0021 0.0014 0.0015 0.0011 0.0012 0.0012 0.0016 hexCer(d18:1/16:0) 0.1122 0.0983 0.1055 0.1486 0.1169 0.0620 0.0493 0.0505 0.0496 0.0656 hexCer(d18:1/18:0) 0.0243 0.0220 0.0247 0.0351 0.0307 0.0120 0.0097 0.0096 0.0099 0.0128 hexCer(d18:1/20:0) 0.0042 0.0036 0.0045 0.0061 0.0058 0.0070 0.0058 0.0058 0.0059 0.0072 hexCer(d18:1/22:0) 0.0302 0.0282 0.0342 0.0444 0.0475 0.0326 0.0270 0.0265 0.0271 0.0339 hexCer(d18:1/23:0) 0.0076 0.0076 0.0094 0.0128 0.0134 0.0082 0.0066 0.0068 0.0067 0.0083 hexCer(d18:1/24:0) 0.0408 0.0382 0.0461 0.0630 0.0700 0.0432 0.0346 0.0349 0.0337 0.0427 hexCer(d18:1/24:1) 0.0375 0.0369 0.0427 0.0578 0.0532 0.0495 0.0417 0.0405 0.0402 0.0527 hexCer(d18:1/24:2) 0.0037 0.0036 0.0042 0.0055 0.0049 0.0049 0.0042 0.0040 0.0039 0.0051 hexCer(d18:1/25:0) 0.0008 0.0008 0.0010 0.0013 0.0014 0.0012 0.0010 0.0010 0.0009 0.0012 hexCer(d18:1/25:1) 0.0009 0.0008 0.0010 0.0014 0.0014 0.0019 0.0016 0.0015 0.0015 0.0020 hexCer(d18:1/25:2) 0.0002 0.0002 0.0002 0.0002 0.0002 0.0003 0.0003 0.0002 0.0003 0.0004 hexCer(d18:1/26:0) 0.0003 0.0003 0.0003 0.0005 0.0005 0.0005 0.0004 0.0004 0.0004 0.0006 hexCer(d18:1/26:1) 0.0006 0.0006 0.0007 0.0010 0.0010 0.0018 0.0016 0.0015 0.0014 0.0021 hexCer(d18:1/26:2) 0.0002 0.0002 0.0002 0.0003 0.0003 0.0006 0.0005 0.0004 0.0005 0.0007 hexCer(d18:2/16:0) 0.0025 0.0021 0.0023 0.0035 0.0024 0.0010 0.0008 0.0008 0.0008 0.0011 hexCer(d18:2/18:0) 0.0020 0.0018 0.0018 0.0029 0.0020 0.0005 0.0004 0.0005 0.0004 0.0006 hexCer(d18:2/20:0) 0.0004 0.0004 0.0004 0.0006 0.0004 0.0004 0.0003 0.0003 0.0003 0.0004 hexCer(d18:2/22:0) 0.0035 0.0038 0.0041 0.0054 0.0043 0.0020 0.0016 0.0015 0.0016 0.0020 hexCer(d18:2/23:0) 0.0006 0.0008 0.0009 0.0011 0.0009 0.0004 0.0003 0.0003 0.0003 0.0004 hexCer(d18:2/23:1) 0.0002 0.0002 0.0003 0.0003 0.0003 0.0002 0.0001 0.0001 0.0001 0.0002 PE(16:0p/18:2) 0.0205 0.0156 0.0162 0.0202 0.0179 0.0095 0.0106 0.0100 0.0080 0.0080 PE(16:0p/20:1) 0.0069 0.0064 0.0051 0.0063 0.0084 0.0076 0.0083 0.0069 0.0059 PE(16:0p/20:2) 0.0065 0.0054 0.0068 0.0066 0.0071 0.0044 0.0055 0.0051 0.0057 0.0043 PE(16:0p/20:3) 0.0442 0.0376 0.0358 0.0314 0.0383 0.0185 0.0185 0.0161 0.0164 0.0131 PE(16:0p/20:4) 0.8379 0.6829 0.7074 0.6702 0.6831 0.2842 0.2771 0.2775 0.2886 0.2364 PE(16:0p/22:4) 0.1590 0.1352 0.1368 0.1225 0.1586 0.1313 0.1288 0.1122 0.1256 0.1051 PE(16:0p/22:5) 0.2954 0.2494 0.2519 0.2128 0.2595 0.2397 0.2485 0.2337 0.2374 0.2040 PE(16:0p/22:6) 0.3877 0.3285 0.3238 0.3146 0.3439 0.3453 0.3489 0.3224 0.3431 0.2983 PE(18:0p/18:1) 0.3984 0.3350 0.3398 0.3499 0.4360 0.1827 0.1732 0.1701 0.1675 0.1458 PE(18:0p/18:2) 0.0222 0.0243 0.0214 0.0218 0.0232 0.0154 0.0172 0.0138 0.0135 0.0116 PE(18:0p/18:3) 0.0021 0.0021 0.0032 0.0024 0.0034 0.0016 0.0012 0.0014 0.0017 0.0013 PE(18:0p/20:3) 0.0404 0.0299 0.0318 0.0295 0.0330 0.0146 0.0172 0.0163 0.0145 0.0135 PE(18:0p/20:4) 1.5806 1.3529 1.4713 1.3934 1.4753 0.5877 0.5646 0.5059 0.5053 0.4707 PE(18:0p/20:5) 0.1398 0.1197 0.1245 0.1279 0.1314 0.0694 0.0717 0.0658 0.0688 0.0621 PE(18:0p/22:6) 0.4549 0.3930 0.4150 0.5292 0.4542 0.4574 0.4260 0.3900 0.4042 0.4179 PE(18:0p/24:6) 0.0051 0.0064 0.0046 0.0055 0.0055 0.0053 0.0048 0.0051 0.0050 0.0049 PE(30:0) 0.0044 0.0032 0.0034 0.0055 0.0038 0.0106 0.0079 0.0066 0.0076 0.0088 PE(30:1) 0.0043 0.0032 0.0031 0.0053 0.0035 0.0077 0.0060 0.0049 0.0060 0.0071 PE(32:0) 0.0200 0.0171 0.0194 0.0161 0.0303 0.0359 0.0420 0.0280 0.0405 0.0446 PE(32:1) 0.0956 0.0753 0.0749 0.1133 0.0850 0.1480 0.1273 0.1215 0.1319 0.1397 PE(34:0) 0.0331 0.0348 0.0252 0.0451 0.0433 0.0800 0.0543 0.0589 0.0580 0.0669 PE(34:1) 0.8555 0.6029 0.7022 0.8263 0.7596 0.8349 0.8285 0.7944 0.7857 0.7712 PE(34:2) 0.2073 0.1750 0.1657 0.2164 0.1751 0.2740 0.2895 0.2773 0.2702 0.2744 PE(36:0) 0.0187 0.0225 0.0144 0.0179 0.0230 0.0265 0.0197 0.0125 0.0196 0.0250 PE(36:1) 0.9029 0.7177 0.8202 0.8161 0.9120 0.9222 0.9388 0.9390 0.8679 0.8521 PE(36:2) 0.8331 0.6983 0.6822 0.7286 0.7282 1.0418 1.0278 1.0505 0.9825 0.9605 PE(36:3) 0.2043 0.1537 0.1637 0.1850 0.1693 0.2116 0.2033 0.1905 0.1841 0.1924 PE(36:4) 0.2469 0.2052 0.1844 0.1761 0.1914 0.1281 0.1370 0.1345 0.1346 0.1196 PE(36:5) 0.0514 0.0383 0.0394 0.0411 0.0407 0.0323 0.0384 0.0364 0.0354 0.0316 PE(38:2) 0.0296 0.0618 0.0572 0.0572 0.0520 0.0803 0.0804 0.0704 0.0568 0.0702 PE(38:3) 0.3233 0.3150 0.3096 0.2706 0.3011 0.2073 0.2403 0.2314 0.2218 0.1969 PE(38:4) 1.5513 1.4056 1.2127 1.0543 1.3557 0.9165 0.9405 0.9512 0.8573 0.7648 PE(38:5) 0.4878 0.4033 0.3870 0.3593 0.3779 0.3874 0.4220 0.4341 0.3828 0.3563 PE(38:6) 0.2883 0.2336 0.2153 0.1895 0.2231 0.1876 0.1817 0.1812 0.1836 0.1534 PE(40:4) 0.2290 0.2024 0.1700 0.1581 0.2056 0.1383 0.1380 0.1338 0.1245 0.1136 PE(40:5) 0.3065 0.2595 0.2497 0.2087 0.2642 0.1912 0.2048 0.2021 0.1774 0.1569 PE(40:6) 0.3947 0.3012 0.3235 0.2412 0.3365 0.2475 0.2623 0.2633 0.2331 0.2077 PE(40:7) 0.1994 0.1880 0.1503 0.1167 0.1512 0.1444 0.1620 0.1628 0.1522 0.1332 PE(40:8) 0.0259 0.0247 0.0186 0.0128 0.0207 0.0163 0.0171 0.0179 0.0160 0.0140 PG(34:1) 0.5169 0.4034 0.3710 0.5395 0.4531 0.5986 0.5621 0.7115 0.6501 0.7312 PG(34:2) 0.0326 0.0320 0.0272 0.0354 0.0275 0.0434 0.0411 0.0460 0.0365 0.0484 PG(36:1) 0.3161 0.2463 0.2647 0.2878 0.3487 0.3240 0.2751 0.3851 0.3051 0.3362 PG(36:2) 0.4551 0.3618 0.3587 0.4543 0.4447 0.2904 0.2925 0.3392 0.2889 0.2832 PG(38:2) 0.0046 0.0043 0.0034 0.0040 0.0067 0.0086 0.0080 0.0067 0.0057 PG(38:3) 0.0187 0.0198 0.0190 0.0274 0.0203 0.0146 0.0166 0.0175 0.0204 0.0219 PI(34:1) 0.0403 0.0356 0.0379 0.0370 0.0407 0.0510 0.0578 0.0574 0.0596 0.0655 PI(34:2) 0.0175 0.0152 0.0158 0.0173 0.0161 0.0282 0.0325 0.0329 0.0301 0.0342 PI(36:1) 0.0350 0.0323 0.0360 0.0318 0.0416 0.0424 0.0495 0.0590 0.0452 0.0507 PI(36:2) 0.0554 0.0586 0.0675 0.0625 0.0593 0.0949 0.0910 0.1092 0.0977 0.1144 PI(36:3) 0.0336 0.0321 0.0365 0.0329 0.0303 0.0372 0.0376 0.0407 0.0340 0.0348 PI(38:2) 0.0072 0.0047 0.0057 0.0038 0.0051 0.0115 0.0119 0.0103 0.0130 0.0099 PI(38:3) 0.0312 0.0139 0.0207 0.0448 0.0417 0.0619 0.0680 0.0454 0.0508 PI(38:4) 0.3477 0.4054 0.4882 0.5331 0.4899 0.3257 0.4658 0.4276 0.4136 0.4093 PI(38:5) 0.1078 0.0826 0.1040 0.0985 0.0994 0.1408 0.2040 0.1545 0.1228 0.1625 PI(40:4) 0.0158 0.0138 0.0182 0.0216 0.0210 0.0209 0.0232 0.0231 0.0182 0.0214 PI(40:5) 0.0563 0.0585 0.0631 0.0633 0.0574 0.0609 0.0684 0.0670 0.0599 0.0684 PI(40:6) 0.0283 0.0263 0.0277 0.0310 0.0279 0.0335 0.0351 0.0339 0.0331 0.0374 PI(40:7) 0.0073 0.0061 0.0068 0.0071 0.0053 0.0063 0.0069 0.0082 0.0074 0.0088 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name pubchem_id inchi_key kegg_id other_id other_id_type ri ri_type moverz_quant Cer(d18:0/14:0) 1.55 Cer(d18:0/16:0) 1.53 Cer(d18:0/18:0) 1.53 Cer(d18:0/18:1) 1.53 Cer(d18:0/20:0) 1.52 Cer(d18:0/22:0) 1.5 Cer(d18:0/23:0) 1.5 Cer(d18:0/24:0) 1.49 Cer(d18:0/24:1) 1.49 Cer(d18:0/24:2) 1.51 Cer(d18:0/24:3) 1.48 Cer(d18:0/25:0) 1.49 Cer(d18:0/25:1) 1.48 Cer(d18:0/25:2) 1.48 Cer(d18:0/26:0) 1.53 Cer(d18:0/26:1) 1.48 Cer(d18:0/26:2) 1.46 Cer(d18:1/14:0) 1.54 Cer(d18:1/16:0) 1.53 Cer(d18:1/18:0) 1.52 Cer(d18:1/18:1) 1.51 Cer(d18:1/20:0) 1.51 Cer(d18:1/22:0) 1.5 Cer(d18:1/23:0) 1.49 Cer(d18:1/24:0) 1.49 Cer(d18:1/24:1) 1.48 Cer(d18:1/24:2) 1.48 Cer(d18:1/24:3) 1.48 Cer(d18:1/25:0) 1.5 Cer(d18:1/25:1) 1.47 Cer(d18:1/25:2) 1.47 Cer(d18:1/26:0) 1.47 Cer(d18:1/26:1) 1.47 Cer(d18:1/26:2) 1.47 Cer(d18:2/14:0) 1.53 Cer(d18:2/16:0) 1.53 Cer(d18:2/18:0) 1.51 Cer(d18:2/18:1) 1.52 Cer(d18:2/20:0) 1.5 Cer(d18:2/21:0) 1.49 Cer(d18:2/22:0) 1.49 Cer(d18:2/23:0) 1.47 Cer(d18:2/23:1) 1.48 Cer(d18:2/24:0) 1.46 Cer(d18:2/24:1) 1.48 Cer(d18:2/24:2) 1.47 Cer(d18:2/24:3) 1.45 Cer(d18:2/25:0) 1.46 Cer(d18:2/25:1) 1.47 Cer(d18:2/25:2) 1.5 Cer(d18:2/26:0) 1.46 Cer(d18:2/26:1) 1.46 Cer(d18:2/26:2) 1.46 hex2Cer(d18:0/14:0) 5.22 hex2Cer(d18:0/16:0) 5.28 hex2Cer(d18:0/18:0) 5.25 hex2Cer(d18:0/22:0) 5.23 hex2Cer(d18:1/14:0) 5.31 hex2Cer(d18:1/16:0) 5.28 hex2Cer(d18:1/18:0) 5.25 hex2Cer(d18:1/20:0) 5.2 hex2Cer(d18:1/22:0) 5.2 hex2Cer(d18:1/23:0) 5.2 hex2Cer(d18:1/24:0) 5.2 hex2Cer(d18:1/24:1) 5.21 hex2Cer(d18:1/24:2) 5.21 hex2Cer(d18:1/25:0) 5.18 hex2Cer(d18:1/25:1) 5.2 hex2Cer(d18:1/25:2) 5.06 hex2Cer(d18:1/26:0) 5.2 hex2Cer(d18:1/26:1) 5.18 hex2Cer(d18:1/26:2) 5.17 hex2Cer(d18:2/16:0) 5.28 hex2Cer(d18:2/18:0) 5.24 hex2Cer(d18:2/20:0) 5.22 hex2Cer(d18:2/22:0) 5.2 hex2Cer(d18:2/23:0) 5.19 hex2Cer(d18:2/23:1) 5.2 hexCer(d16:1/20:0) 3.27 hexCer(d16:1/22:0) 3.19 hexCer(d18:0/14:0) 3.46 hexCer(d18:0/16:0) 3.39 hexCer(d18:0/18:0) 3.28 hexCer(d18:0/18:1) 3.29 hexCer(d18:0/20:0) 3.2 hexCer(d18:0/22:0) 3.12 hexCer(d18:0/24:0) 3.09 hexCer(d18:0/24:1) 3.1 hexCer(d18:0/24:2) 3.07 hexCer(d18:0/25:0) 3.1 hexCer(d18:0/25:1) 3.09 hexCer(d18:0/25:2) 3.07 hexCer(d18:0/26:1) 3.01 hexCer(d18:0/26:2) 3.07 hexCer(d18:1/14:0) 3.52 hexCer(d18:1/16:0) 3.37 hexCer(d18:1/18:0) 3.28 hexCer(d18:1/20:0) 3.22 hexCer(d18:1/22:0) 3.12 hexCer(d18:1/23:0) 3.06 hexCer(d18:1/24:0) 3.07 hexCer(d18:1/24:1) 3.08 hexCer(d18:1/24:2) 3.12 hexCer(d18:1/25:0) 3.05 hexCer(d18:1/25:1) 3.05 hexCer(d18:1/25:2) 3.05 hexCer(d18:1/26:0) 3.01 hexCer(d18:1/26:1) 3.04 hexCer(d18:1/26:2) 3.11 hexCer(d18:2/16:0) 3.37 hexCer(d18:2/18:0) 3.31 hexCer(d18:2/20:0) 3.22 hexCer(d18:2/22:0) 3.11 hexCer(d18:2/23:0) 3.05 hexCer(d18:2/23:1) 3.07 PE(16:0p/18:2) 6.64 PE(16:0p/20:1) 6.62 PE(16:0p/20:2) 6.6 PE(16:0p/20:3) 6.56 PE(16:0p/20:4) 6.52 PE(16:0p/22:4) 6.51 PE(16:0p/22:5) 6.55 PE(16:0p/22:6) 6.5 PE(18:0p/18:1) 6.61 PE(18:0p/18:2) 6.61 PE(18:0p/18:3) 6.57 PE(18:0p/20:3) 6.48 PE(18:0p/20:4) 6.48 PE(18:0p/20:5) 6.48 PE(18:0p/22:6) 6.44 PE(18:0p/24:6) 6.45 PE(30:0) 6.8 PE(30:1) 6.79 PE(32:0) 6.77 PE(32:1) 6.74 PE(34:0) 6.72 PE(34:1) 6.72 PE(34:2) 6.7 PE(36:0) 6.67 PE(36:1) 6.67 PE(36:2) 6.65 PE(36:3) 6.66 PE(36:4) 6.62 PE(36:5) 6.59 PE(38:2) 6.63 PE(38:3) 6.6 PE(38:4) 6.56 PE(38:5) 6.57 PE(38:6) 6.59 PE(40:4) 6.58 PE(40:5) 6.58 PE(40:6) 6.56 PE(40:7) 6.52 PE(40:8) 6.55 PG(34:1) 5.47 PG(34:2) 5.46 PG(36:1) 5.44 PG(36:2) 5.44 PG(38:2) 5.44 PG(38:3) 5.42 PI(34:1) 5.73 PI(34:2) 5.7 PI(36:1) 5.7 PI(36:2) 5.69 PI(36:3) 5.69 PI(38:2) 5.67 PI(38:3) 5.66 PI(38:4) 5.65 PI(38:5) 5.65 PI(40:4) 5.65 PI(40:5) 5.65 PI(40:6) 5.65 PI(40:7) 5.65 METABOLITES_END #END