#METABOLOMICS WORKBENCH Havefars_20240906_033017 DATATRACK_ID:5175 STUDY_ID:ST003622 ANALYSIS_ID:AN005950 PROJECT_ID:PR002238 VERSION 1 CREATED_ON December 12, 2024, 9:21 am #PROJECT PR:PROJECT_TITLE A multi-omic census reveals obesity-associated microRNA miR-let-7 as novel PR:PROJECT_TITLE instigator of adipose mitochondrial dysfunction and of intergenerational PR:PROJECT_TITLE metabolic decline. PR:PROJECT_SUMMARY We here describe that obesity and weight loss in male mice causes reversible PR:PROJECT_SUMMARY abnormalities in glucose and lipid metabolism, serum metabolomes, and white PR:PROJECT_SUMMARY adipose tissue alongside reversible reductions in activity of genes controlling PR:PROJECT_SUMMARY mitochondrial energy dissipation. When mating obese male mice with lean females, PR:PROJECT_SUMMARY we observed concordant reductions in mitochondrial gene expression and PR:PROJECT_SUMMARY translation in offspring that resemble those observed in the paternal (F0) PR:PROJECT_SUMMARY generation. When mapping miRNA responses across somatic and gametic cell types PR:PROJECT_SUMMARY and generations, we found that obesity and weight loss reversible affected miRNA PR:PROJECT_SUMMARY abundance, and observed miR-let7 isoforms induced in obese adipose tissues of F0 PR:PROJECT_SUMMARY and offspring (F1) generations, as well as in sperm of obese F0 mice. PR:PROJECT_SUMMARY Mechanistically, when overexpressing miR-let-7 in adipocytes, we found it to PR:PROJECT_SUMMARY silence DICER1, a cellular rheostat required for adipose tissue adaptation in PR:PROJECT_SUMMARY obesity as evidenced by functional deficiency in mitochondrial functioon PR:PROJECT_SUMMARY following DICER1 loss. Delivery of miR-let-7 into oocytes elicited glucose PR:PROJECT_SUMMARY intolerance and impairments in adipose mitochondrial gene expression in mice PR:PROJECT_SUMMARY sired from miRNA-injected embryos, phenocopying aspects of paternal obesity. PR:PROJECT_SUMMARY When performing single-cell RNA-Seq of embryos, we found that miR-let7 impaired PR:PROJECT_SUMMARY mitochondrial gene expression, suggesting altered energy metabolism following PR:PROJECT_SUMMARY sperm-mediated changes in zygotic miRNAs. When studying miRNA alterations in PR:PROJECT_SUMMARY human semen, we lifestyle-induced weight loss to downregulate MIR-LET-7 in human PR:PROJECT_SUMMARY subjects, suggesting similar roles for human MIR-LET-7 in gametic epigenomes and PR:PROJECT_SUMMARY embryogenesis. PR:INSTITUTE University of Southern Denmark PR:DEPARTMENT Department of Biochemistry and Molecular Biology PR:LAST_NAME Kornfeld PR:FIRST_NAME Jan-Wilhelm PR:ADDRESS University of Southern Denmark (SDU), Campusvej 55, 5230 Odense M, Denmark PR:EMAIL janwilhelmkornfeld@bmb.sdu.dk PR:PHONE +4565503904 #STUDY ST:STUDY_TITLE A multi-omic census reveals obesity-associated microRNA miR-let-7 as novel ST:STUDY_TITLE instigator of adipose mitochondrial dysfunction and of intergenerational ST:STUDY_TITLE metabolic decline. ST:STUDY_SUMMARY We here describe that obesity and weight loss in male mice causes reversible ST:STUDY_SUMMARY abnormalities in glucose and lipid metabolism, serum metabolomes, and white ST:STUDY_SUMMARY adipose tissue alongside reversible reductions in activity of genes controlling ST:STUDY_SUMMARY mitochondrial energy dissipation. When mating obese male mice with lean females, ST:STUDY_SUMMARY we observed concordant reductions in mitochondrial gene expression and ST:STUDY_SUMMARY translation in offspring that resemble those observed in the paternal (F0) ST:STUDY_SUMMARY generation. When mapping miRNA responses across somatic and gametic cell types ST:STUDY_SUMMARY and generations, we found that obesity and weight loss reversible affected miRNA ST:STUDY_SUMMARY abundance, and observed miR-let7 isoforms induced in obese adipose tissues of F0 ST:STUDY_SUMMARY and offspring (F1) generations, as well as in sperm of obese F0 mice. ST:STUDY_SUMMARY Mechanistically, when overexpressing miR-let-7 in adipocytes, we found it to ST:STUDY_SUMMARY silence DICER1, a cellular rheostat required for adipose tissue adaptation in ST:STUDY_SUMMARY obesity as evidenced by functional deficiency in mitochondrial functioon ST:STUDY_SUMMARY following DICER1 loss. Delivery of miR-let-7 into oocytes elicited glucose ST:STUDY_SUMMARY intolerance and impairments in adipose mitochondrial gene expression in mice ST:STUDY_SUMMARY sired from miRNA-injected embryos, phenocopying aspects of paternal obesity. ST:STUDY_SUMMARY When performing single-cell RNA-Seq of embryos, we found that miR-let7 impaired ST:STUDY_SUMMARY mitochondrial gene expression, suggesting altered energy metabolism following ST:STUDY_SUMMARY sperm-mediated changes in zygotic miRNAs. When studying miRNA alterations in ST:STUDY_SUMMARY human semen, we lifestyle-induced weight loss to downregulate MIR-LET-7 in human ST:STUDY_SUMMARY subjects, suggesting similar roles for human MIR-LET-7 in gametic epigenomes and ST:STUDY_SUMMARY embryogenesis. ST:INSTITUTE University of Southern Denmark ST:LAST_NAME Kornfeld ST:FIRST_NAME Jan-Wilhelm ST:ADDRESS University of Southern Denmark (SDU), Campusvej 55, 5230 Odense M, Denmark ST:EMAIL janwilhelmkornfeld@bmb.sdu.dk ST:PHONE +4565503904 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS Blank01 IEI_Blank01 Sample source:Blank | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_Blank01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_Blank01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_Blank01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_Blank01.mzML SUBJECT_SAMPLE_FACTORS Blank02 IEI_Blank02 Sample source:Blank | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_Blank02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_Blank02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_Blank02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_Blank02.mzML SUBJECT_SAMPLE_FACTORS Blank03 IEI_Blank03 Sample source:Blank | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_Blank03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_Blank03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_Blank03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_Blank03.mzML SUBJECT_SAMPLE_FACTORS HFD01 IEI_HFD01 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD01.mzML SUBJECT_SAMPLE_FACTORS HFD02 IEI_HFD02 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD02.mzML SUBJECT_SAMPLE_FACTORS HFD03 IEI_HFD03 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD03.mzML SUBJECT_SAMPLE_FACTORS HFD04 IEI_HFD04 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD04.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD04.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD04.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD04.mzML SUBJECT_SAMPLE_FACTORS HFD05 IEI_HFD05 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD05.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD05.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD05.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD05.mzML SUBJECT_SAMPLE_FACTORS HFD06 IEI_HFD06 Sample source:Serum | Diet:HFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_HFD06.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_HFD06.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_HFD06.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_HFD06.mzML SUBJECT_SAMPLE_FACTORS LFD01 IEI_LFD01 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD01.mzML SUBJECT_SAMPLE_FACTORS LFD02 IEI_LFD02 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD02.mzML SUBJECT_SAMPLE_FACTORS LFD03 IEI_LFD03 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD03.mzML SUBJECT_SAMPLE_FACTORS LFD04 IEI_LFD04 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD04.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD04.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD04.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD04.mzML SUBJECT_SAMPLE_FACTORS LFD05 IEI_LFD05 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD05.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD05.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD05.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD05.mzML SUBJECT_SAMPLE_FACTORS LFD06 IEI_LFD06 Sample source:Serum | Diet:LFD RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_LFD06.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_LFD06.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_LFD06.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_LFD06.mzML SUBJECT_SAMPLE_FACTORS QC01 IEI_QC01 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_QC01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_QC01.mzML SUBJECT_SAMPLE_FACTORS QC02 IEI_QC02 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_QC02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_QC02.mzML SUBJECT_SAMPLE_FACTORS QC03 IEI_QC03 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_QC03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_QC03.mzML SUBJECT_SAMPLE_FACTORS QC04 IEI_QC04 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC04.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC04.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_QC04.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_QC04.mzML SUBJECT_SAMPLE_FACTORS QC05 IEI_QC05 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC05.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC05.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_QC05.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_QC05.mzML SUBJECT_SAMPLE_FACTORS QC06 IEI_QC06 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC06.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC06.mzML; RAW_FILE_NAME_METABOPOS=-; RAW_FILE_NAME_METABONEG=- SUBJECT_SAMPLE_FACTORS QC07 IEI_QC07 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC07.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC07.mzML; RAW_FILE_NAME_METABOPOS=-; RAW_FILE_NAME_METABONEG=- SUBJECT_SAMPLE_FACTORS QC08 IEI_QC08 Sample source:QC | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_QC08.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_QC08.mzML; RAW_FILE_NAME_METABOPOS=-; RAW_FILE_NAME_METABONEG=- SUBJECT_SAMPLE_FACTORS QC09 IEI_REV01 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV01.mzML SUBJECT_SAMPLE_FACTORS REV02 IEI_REV02 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV02.mzML SUBJECT_SAMPLE_FACTORS REV03 IEI_REV03 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV03.mzML SUBJECT_SAMPLE_FACTORS REV04 IEI_REV04 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV04.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV04.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV04.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV04.mzML SUBJECT_SAMPLE_FACTORS REV05 IEI_REV05 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV05.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV05.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV05.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV05.mzML SUBJECT_SAMPLE_FACTORS REV06 IEI_REV06 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV06.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV06.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV06.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV06.mzML SUBJECT_SAMPLE_FACTORS REV07 IEI_REV07 Sample source:Serum | Diet:REV RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_REV07.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_REV07.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_REV07.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_REV07.mzML SUBJECT_SAMPLE_FACTORS MSMS01 IEI_MSMS01 Sample source:Serum | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_MSMS01.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_MSMS01.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_MSMS01.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_MSMS01.mzML SUBJECT_SAMPLE_FACTORS MSMS02 IEI_MSMS02 Sample source:Serum | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_MSMS02.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_MSMS02.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_MSMS02.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_MSMS02.mzML SUBJECT_SAMPLE_FACTORS MSMS03 IEI_MSMS03 Sample source:Serum | Diet:- RAW_FILE_NAME_LIPIDPOS=IEI_lipid_pos_MSMS03.mzML; RAW_FILE_NAME_LIPIDNEG=IEI_lipid_neg_MSMS03.mzML; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_MSMS03.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_MSMS03.mzML SUBJECT_SAMPLE_FACTORS MSMS04 IEI_MSMS04 Sample source:Serum | Diet:- RAW_FILE_NAME_LIPIDPOS=-; RAW_FILE_NAME_LIPIDNEG=-; RAW_FILE_NAME_METABOPOS=IEI_metabo_pos_MSMS04.mzML; RAW_FILE_NAME_METABONEG=IEI_metabo_neg_MSMS04.mzML #COLLECTION CO:COLLECTION_SUMMARY For serum collection, Blood collected by the cardiac puncture was centrifuged at CO:COLLECTION_SUMMARY 2,000 g for 15 min CO:SAMPLE_TYPE Blood (serum) CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY All animal experiments were approved by the Ministry of Environment and TR:TREATMENT_SUMMARY Agriculture Denmark (Miljø- og Fødevarestyrelsen), the license no. TR:TREATMENT_SUMMARY 2018-15-0201-01544. All mice were housed under a 12-h light/ 12-h dark cycle in TR:TREATMENT_SUMMARY a temperature and humidity-controlled facility and had ad libitum access to TR:TREATMENT_SUMMARY diets and drinking water. 4-week-old C57BL/6J male mice (Janvier Labs) were fed TR:TREATMENT_SUMMARY with a chow diet (NIH-31, Zeigler Brothers Inc., 8% calories from fat) for 2 TR:TREATMENT_SUMMARY weeks of acclimatization and then were fed with either a low-fat diet (LFD, TR:TREATMENT_SUMMARY D12450J, 10% kcal from fat, Research Diet) or a high-fat diet (HFD, D12492, 60% TR:TREATMENT_SUMMARY kcal from fat, Research Diet) for 9 weeks. After 9 weeks of feeding, half of TR:TREATMENT_SUMMARY HFD-fed mice were randomly assigned to the diet regression group which was given TR:TREATMENT_SUMMARY LFD (REV) group. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 100 µL of serum was mixed with 1000 µL of a 2:1 chloroform/methanol solution SP:SAMPLEPREP_SUMMARY and 200 µL of water. Four blank samples, each containing 100 µL of water, were SP:SAMPLEPREP_SUMMARY processed in parallel. The mixtures were shaken at 1000 rpm for 30 minutes at SP:SAMPLEPREP_SUMMARY 4°C, followed by centrifugation at 16,000g for 10 minutes at 4°C to separate SP:SAMPLEPREP_SUMMARY the phases. The aqueous phase was re-extracted with 350 µL of an 86:14:1 SP:SAMPLEPREP_SUMMARY chloroform/methanol/water solution. The organic phase from this re-extraction SP:SAMPLEPREP_SUMMARY was combined with the corresponding organic phase from the initial extraction. SP:SAMPLEPREP_SUMMARY Aqueous fraction was dried using SpeedVac, while the organic phase was dried SP:SAMPLEPREP_SUMMARY under a stream of nitrogen. For subsequent analysis, the dried aqueous fractions SP:SAMPLEPREP_SUMMARY were reconstituted in 30 µL of 1% formic acid for metabolomics. The organic SP:SAMPLEPREP_SUMMARY phase was reconstituted in 30 µL of lipidomics solvent A (5:1:4 SP:SAMPLEPREP_SUMMARY isopropanol/methanol/water with 5 mM ammonium acetate and 0.1% acetic acid). A SP:SAMPLEPREP_SUMMARY pooled quality control (QC) sample was prepared for each analytical setup by SP:SAMPLEPREP_SUMMARY combining 5 µL from each sample, excluding blanks #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Lipidomics CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1290 CH:COLUMN_NAME Agilent ZORBAX Eclipse Plus C18 (50 x 2.1mm,1.8um) CH:SOLVENT_A 95% isopropanol/1% methanol/4% water; 5 mM ammonium acetate; 0.1% acetic acid CH:SOLVENT_B 99% isopropanol/1% water; 5 mM ammonium acetate; 0.1% acetic acid CH:FLOW_GRADIENT 0% B from 0 to 1 min, 0-25% B from 1 to 1.5 min, 25-95% B from 1.5 to 12 min, CH:FLOW_GRADIENT 95% B from 12 to 14 min, and 95-0% B from 14 to 15 min, followed by a 3-minute CH:FLOW_GRADIENT equilibration CH:FLOW_RATE 400 uL/min CH:COLUMN_TEMPERATURE 50 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6530 QTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS Lipidomics: Data were acquired in MS-only mode, while MS/MS spectra were MS:MS_COMMENTS obtained exclusively from a pooled sample for annotation. Scan range: 50-1700 MS:MS_COMMENTS CID energy: 40V All data was converted. mzML format using ProteoWizard. Data was MS:MS_COMMENTS annotated in MS-Dial (v. 4.9) against the incorporated lipid-blast database with MS:MS_COMMENTS an MS1/MS2 mass tolerance of 0.005/0.01 Da and a minimum identification score of MS:MS_COMMENTS 70%. The annotated compounds were exported to PCDL manager B.08.00 (Agilent MS:MS_COMMENTS Technologies) to create a database for area extraction in Profinder 10.0 MS:MS_COMMENTS (Agilent Technologies). Features with signals less than 5 times those in blanks MS:MS_COMMENTS or missing in more than 20% of QC samples were removed and signals were QC MS:MS_COMMENTS corrected #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak intensity MS_METABOLITE_DATA_START Samples IEI_Blank01 IEI_Blank02 IEI_Blank03 IEI_HFD01 IEI_HFD02 IEI_HFD03 IEI_HFD04 IEI_HFD05 IEI_HFD06 IEI_LFD01 IEI_LFD02 IEI_LFD03 IEI_LFD04 IEI_LFD05 IEI_LFD06 IEI_QC01 IEI_QC02 IEI_QC03 IEI_QC04 IEI_QC05 IEI_QC06 IEI_QC07 IEI_QC08 IEI_REV01 IEI_REV02 IEI_REV03 IEI_REV04 IEI_REV05 IEI_REV06 IEI_REV07 Factors Sample source:Blank | Diet:- Sample source:Blank | Diet:- Sample source:Blank | Diet:- Sample source:Serum | Diet:HFD Sample source:Serum | Diet:HFD Sample source:Serum | Diet:HFD Sample source:Serum | Diet:HFD Sample source:Serum | Diet:HFD Sample source:Serum | Diet:HFD Sample source:Serum | Diet:LFD Sample source:Serum | Diet:LFD Sample source:Serum | Diet:LFD Sample source:Serum | Diet:LFD Sample source:Serum | Diet:LFD Sample source:Serum | Diet:LFD Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:QC | Diet:- Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV Sample source:Serum | Diet:REV FAHFA 2:0_18:3 3286.787069 3542.533416 2990.887259 20150.25215 31493.23431 23194.0238 31382.72015 27782.33628 50941.20299 192730.3336 123478.5946 84899.13616 116749.773 181571.5023 94954.74806 113976.1087 106341.1952 116867.5964 116054.8352 112360.4501 110126.3819 105121.6756 89490.86741 175900.0062 215753.4299 140356.057 254789.275 154280.1924 162435.7362 172829.3281 FAHFA 2:0_20:4 172367.2565 208457.9512 198175.4731 243919.7515 185205.4178 268158.2928 265986.2161 206160.2629 236587.201 246127.3788 189460.5007 154390.3987 202490.4624 198151.8987 204590.0649 198402.36 200458.9249 196579.6098 191794.5484 175235.5636 194606.4592 222709.5776 188737.7683 255946.0674 225284.2307 167107.6755 220949.0141 LPE 16:0 35404.44922 37481.70703 32245.07031 41263.42188 47811.82813 48168.76172 31276.29883 29289.80469 50080.24609 56470.32422 52583.60938 54007.1875 47037.14453 43246.92188 48807.29688 51162.56641 48596.82031 51072.18359 46932.13281 37504.18359 62384.66406 65465.06641 52225.25 58904.19922 71734.60156 58412.26953 52495.57422 LPE 18:2 1411.45459 1758.200806 57041.17578 56320.66797 65401.27344 68349.14063 54054.29297 59196.08594 19805.63867 18211.25391 40610.46875 32509.25195 29241.15039 31682.82031 35818.26953 33848.87109 37439.07422 40444.94922 38190.41016 37909.23828 35911.33594 29815.29492 27852.71094 27492.36328 25954.63477 34423.56641 29430.76367 21491.88281 21538.10547 LPE 18:0 29884.49805 30205.22852 27322.52572 35888.34719 32494.68359 32624.51758 11653.19336 10248.73047 18209.83072 17608.66423 21861.74414 21500.40804 23335.97461 20008.56008 21989.66944 24122.85547 22486.37432 22867.07504 21329.1107 17913.60547 26393.29263 26219.49877 21039.12891 21823.6582 19016.12305 24713.46328 17063.21261 LPE 20:4 71878.60156 72509.89063 71031.82813 89282.81461 57737.94922 71614.72792 27840.16992 28995 45954.19922 47302.53426 57605 46690.23828 58311.06641 52636.92969 63818.24219 60868.73047 60740.44141 61058.32813 57552.55859 45469.69922 78730.10938 76345.79688 60141.81619 65309.95313 54028.35156 55299.28516 46540.93359 FAHFA 16:1_18:3 1346.860107 1287.29541 3054.040039 20983.72461 11615.7041 6311.717285 10737.55371 19247.05664 7981.830078 9638.126953 10757.37695 10432.22656 9170.546875 9398.422852 10040.0459 9344.96582 7056.072754 19862.46875 24235.67969 13162.33789 30853.37109 16291.7627 17299.4668 19017.2207 FAHFA 16:0_18:2 17969.68164 22251.67188 21617.54297 26665.22266 20161.88086 31957.38867 40306.02734 36733.36719 29577.03516 33663.75391 36182.875 29437.84766 31314.72266 30290.02148 30888.27148 28943.56641 29122.13086 29127.69922 29520.10547 27901.30469 39469.44141 41363.73047 31250.22852 45557.57813 36080.99609 37013.84766 38231.98828 LPC 16:0/0:0 767084.6346 809963.0303 778064.8156 870516.6598 819879.1062 843075.7416 675114.5 661214.4608 773642.6376 855083.4218 891790.7532 839335.5833 853821.351 810290.2794 838354.5339 869908.1875 838710.7395 883021.7967 823601.7817 764983.3051 971090.9121 1010900.109 915904.9084 905017.8125 885086.9545 992798.3483 835182.7355 LPC 18:2/0:0 479422.6968 516257.024 499713.7485 461989.9285 474361.1783 533642.077 292922.125 269174.9688 413108.3413 424296.1149 409562.0366 419885.6474 422721.88 414087.375 441690.3922 446924.6596 430178.6548 455304.4321 427022.5188 378318.9136 452171.8123 495000.8954 462572.1077 447939.1609 424121.4845 439240.9956 389257.0462 LPC 18:1/0:0 208461.7131 224308.0623 191135.7864 197142.0452 187824.3968 232556.0148 207181.8281 189121.6711 253827.8149 295852.1128 302256.3291 251338.3276 277820.9668 266492.6055 292749.999 284499.9136 282925.9468 291294.7026 270407.9263 237741.0718 436152.2231 439153.9351 384371.3428 359801.8369 314294.1013 406583.1885 323572.6836 FAHFA 18:2_20:4 20236.76953 26879.95703 26188.23242 34877.90625 22366.39648 39723.67969 41141.06641 26569.64648 32702.30078 34066.89453 25031.13281 18067.31836 26444.56055 25243.24023 26891.81641 26121.77344 23894.58398 26292.60547 23186.84961 19673.46484 24590.64453 29801.14063 21819.88672 38159.29688 29646.93164 19429.61914 30275.35547 FAHFA 18:1_20:3 49042.58984 59346.84766 53701.92578 67852.84375 49784.57422 83191.8125 93447.95313 73348.82813 69331.10938 81739.39063 82242.59375 61132.16016 70649.52344 71583.60938 73842.52344 70277.35938 74321 69037.17188 67516.53125 60556.92969 89418.53906 98536.03125 76784.33594 111573.0859 81427.50781 80643.0625 85326.30469 Cer_NS d18:1_16:0 117858.7891 100762.6875 106503.0703 137276.7188 58752.40234 84337.48438 25192.39648 30611.14063 44519.92578 36588.38672 52719.21094 51887.90234 58284.32813 54285.38281 61686.23438 59668.97266 60544.57813 56247.78516 53559.83203 48269.76953 56006.32031 52958.84766 53388.73047 47866.67188 27342.45703 51944.00781 35856.76172 Cer_NDS d18:0_16:0 25651.40264 23814.55649 31208.43492 19538.59745 16732.95627 21514.8957 4923.417162 4157.68721 8094.175797 5072.245404 5333.614504 11003.0161 10797.26203 9818.331212 11194.93606 10085.86717 10690.37773 10390.8465 10010.12223 9154.77409 7095.341968 4910.922967 4510.47021 4839.32202 4359.776277 4109.241904 4315.87002 LPC 20:4/0:0 1036.00061 239412.9222 237529.1406 201359.0469 185092.9844 135567.1094 223705.1406 98633.79688 100580.0313 128951.25 133310.875 157639.8281 135374.3281 182104.1094 167981.375 188399 183101.2031 182307.9531 185604.2656 179359.7969 156780.2031 250360.7813 247229.9688 206805.7656 176704.6406 186137.6719 230994.4844 170424.8594 LPC 20:0/0:0 10007.44434 10404.78809 14631.41309 13747.80859 16960.51953 17792.0293 6850.343262 5997.810547 12577.11328 11552.74707 10179.53125 10177.85645 11327.14355 10153.92188 11301.75293 11537.38965 12619.00977 11565.31934 11031.36914 9545.022461 10427.9008 11543.56055 11411.52734 12032.0752 11033.73535 12499.3457 11332.58008 LPC 22:6/0:0 61780.39453 68836.28125 61849.10938 56450.78516 59875.40234 79061.64063 46767.12109 46072.15234 55298.51172 63187.63281 63879.5625 60522.0625 62368.28906 58602.25391 65592.57031 64738.41406 62848.29688 63618.02734 61806.71094 54760.07422 75674.54688 87530.26563 68713.01563 69131.66406 66201.54688 74938.25 55865.98828 Cer_NP t18:0_22:0 22255.64063 22751.49219 26099.5957 36278.17578 22312.42188 26008.18555 5548.883301 7096.736328 8981 11362.81934 10828.60254 12814.1416 12646.11035 12131.85254 13244.93555 12606.85938 12045.83496 13246.19141 12057.00098 11407 11597.66113 9533.18457 8952.510742 8249.883789 6498.660645 10478.02832 5531.258301 Cer_NS d18:1_20:0 41734.92188 40468.12109 43364.89453 76265.38281 29215.2207 36385.5625 6026.754883 6828.044922 12741.30176 12394.11816 19039.03906 12456.9082 20515.50195 18566.09961 22140.58398 20851.05157 21094.5332 20254.89844 20334.79102 17390.50391 26086.15234 21384.26868 19494.55859 16128.1709 12418.00293 18699.00195 13730.05078 Cer_NS d18:1_22:0 285543.375 250154.1094 367929.3125 554468.0028 341723.179 374312.6239 113584.8125 103852.3828 209032.5625 210527.8199 213347.6649 168386.5781 224124.5156 217435.8281 222006.3605 220796.125 216882.5089 217053.1094 205799.8776 185644.9531 218540.1146 215406.6406 196996.125 232572.8569 161923.5469 245661.3125 163966.3516 Cer_NS d18:1_23:0 44063.54609 45167.66202 42592.93056 61481.90215 52584.28925 57830.44739 35700.08393 29043.60162 61211.16552 75979.58371 49044.88481 31036.57132 37042.59745 35918.71308 40674.92178 39725.60113 38690.74098 35658.98934 33304.7757 31948.72786 41622.29814 36685.44838 42024.52066 47462.71935 38226.54411 40855.71876 32823.22789 Cer_NS d18:2_24:1 20124.95584 15674.77295 15836.43555 22604.93945 10087.28855 18174.04306 14474.43359 12555.36244 17104.20503 16367.65463 19992.42111 16896.3418 16219.83105 15860.93848 17069.57639 16464.00781 15459.53418 15347.87981 15781.22375 13627.29883 21972.37909 22763.06865 23595.82102 22653.60547 18776.55587 20746.74708 17140.50977 Cer_NS d18:1_24:1 147570.2031 115661.0547 103235.7988 179736.5368 91070.10926 130948.3359 131802.2656 128896.8194 166243.0313 171516.0313 159959.0303 120457.2109 127788.6792 128295.1406 137453.7262 130042.4397 129652.5736 129493.483 130477.1561 106576.3747 187507.6807 165980.6193 174344.0214 178501.9226 156078.3176 173821.8713 127266.0907 Cer_NS d18:1_24:0 79580.51551 75768.48062 74310.54073 141690.7016 114079.5873 110470.1693 97141.1265 89560.68551 150668.9984 149010.3591 103918.7853 90392.74285 87966.78989 84316.00986 87696.59241 84798.41557 84076.13029 84883.278 87924.68723 70085.82157 97666.54228 99210.28131 88850.73371 136357.6589 111021.4139 127285.3278 77533.23335 Cer_NP t18:0_23:0 1412.481934 1273.782715 1711.731567 22434.83798 25077.91802 27843.9387 34964.30028 21913.02312 26279.86651 8879.562514 9716.029307 16961.59174 20078.47981 15692.79881 16620.32349 14970.5234 14840.02336 15401.90158 15362.55652 15044.17523 15324.35555 14780.81376 11966.56499 14736.73366 11492.78236 12283.27408 10282.5218 8534.496557 12276.76415 7110.434625 PE 16:0_18:2 30127.5625 30680.81641 31469.77516 48836.21931 48072.35156 38829.79688 31813.97461 23194.98047 58577.63672 51705.61802 38970.6099 48410.41016 34349.96094 32678.64258 35156.91346 33668.90234 32757.04688 32592.56836 30235.68555 24798.17302 24314.70808 29109.88477 27710.47121 42640.90234 41848.07813 22696.5957 29632.85352 EtherPE 16:1e_20:4 68371.16406 91255.13281 82462.85938 100153.6563 85304.45313 120262.9688 34581.94531 35965.94141 58385.37891 62963.43359 80590.52344 70845.46875 59460.66016 55529.50391 60710.75391 60318.5 59420.08984 61830.40625 57358.10156 47729.02734 83696.33594 68577.32333 69410.13281 61592.60938 46441.55469 95684.29688 46985.66406 Cer_NP t18:0_24:1 2417.729248 2426.488525 2182.682617 28439.239 26999.23235 32422.04678 38265.22769 26281.84026 32729.97165 10577.61584 10547.42391 20852.95291 22165.94315 16941.86736 24465.53842 17506.26724 18522.20404 20041.66978 18396.99738 19826.78713 18780.61993 17864.24059 14604.6691 20664.89519 14646.41631 16937.10723 14686.02897 15295.48811 15763.658 11307.04057 EtherPE 18:1e_18:2 10882.79392 15334.69296 11990.53714 15517.01363 16745.68394 16634.87236 9440.283203 7907.177734 8303.630711 10472.31738 10531.03714 14492.51953 9166.920189 10178.61453 10053.01694 9720.049956 9841.228113 9396.017729 9069.502076 8412.206055 10919.93262 10606.26465 9929.835845 10229.21777 9221.608398 12772.29108 8858.544922 Cer_NP t18:0_24:0 2064.11792 2039.8573 2343.805908 29974.2095 30260.36471 35303.55201 49298.3308 29467.27806 33314.6418 11657.29346 12628.836 17793.04407 20053.11586 19355.58072 22154.76145 18654.40175 19669.85547 18255.67506 19107.776 18167.37682 17610.75686 17249.70613 16582.76758 23718.0332 16098.37871 16779.49414 15186.27381 11939.91016 17513.45593 8968.46283 EtherPE 18:0e_18:2 11653.96558 18092.58381 14181.72724 18869.84996 23865.18754 21187.27136 8805.296195 7320.986438 11730.38636 11692.10167 11325.59651 14695.05851 11792.93861 11234.09349 11263.04581 12494.73187 11703.90009 10704.06118 11354.34461 9868.424343 11471.70818 11768.25055 11513.98469 11046.9002 11361.05997 13701.0046 9647.29602 PE 16:0_20:4 67796.93502 62036.39491 60438.92536 117550.5602 72114.10321 80802.44265 57362.39676 48399.09094 105932.5759 98458.83929 108250.5796 99534.49678 80708.16751 74547.16352 80766.39501 80715.37225 78169.30684 76778.56645 74201.08837 60775.11083 111347.1778 109649.111 95924.86113 120463.1636 100172.7206 84649.2883 82126.57824 PE 18:1_18:2 44792.59286 44839.48828 45620.07872 72486.69906 54265.76448 53141.15365 29981.08984 22065.50425 48520.94531 42078.83403 34993.53564 36831.82359 35953.62817 34096.57422 36642.25907 35692.08922 35521.75354 34999.86328 32012.64648 27277.4043 29493.53229 28879.03711 30793.00781 46490.80078 39278.38367 23559.21875 26558.6009 PE 18:0_18:2 111872.5249 113863.8065 126804.2755 163048.2274 135422.6293 117785.6299 27355.32122 23660.34962 65286.07797 43725.46702 39058.5167 58074.41768 57863.03533 54548.99417 60584.3195 59116.62854 57406.49704 57366.12858 54577.58297 44958.96756 41175.60578 34224.2029 34122.76813 52559.12629 35530.0004 27355.10931 28574.20789 EtherPE 16:1e_22:6 103354.5479 135525.2311 144968.4903 144207.3798 164100.8774 199349.6094 70951.89844 65761.56704 104996.0391 119137.5391 134474.4531 123758.5929 102996.0343 95065.50781 105885.0938 107808.6875 105095.0246 102552.7909 100612.8973 84168.55352 145834.8281 127964.127 119631.6719 130679.6404 111148.0859 169609.9879 98395.58594 PG 16:0_18:1 8342.630859 8500.113281 7060.640137 10276.6416 8976.804688 77178.2076 5836.723633 11879.02539 8750.021484 5668.350098 7636.660156 8537.818359 10858.3457 10335.3252 10986.00098 11064.09473 11173.14063 10378.79551 10107.5293 8738.526367 6848.455566 20829.078 17047.92578 8321.157227 5608.20381 6512.698242 4413.88623 SM d17:1_16:0 16794.33203 22515.91992 21395.82617 17551.41016 15457.43555 19008.36133 6641.529297 5847.713379 9433.075301 9491.894531 13530.59117 10199.56919 12573.81152 11319.13574 13798.06738 12782.18652 12806.8936 13809.09668 12452.57227 11495.36914 14019.6582 11653.88245 14610.24902 9626.876953 7485.980957 11831.82813 10958.48438 EtherPE 18:2e_20:4 54387.29297 83711.44531 103307.4028 86827.1875 107000.75 140483.575 37870.54688 39312.4375 90606.05469 81423.47656 66690.03906 71366.84375 64807.52719 58103.50831 64687.76266 65087.73438 61865.14844 62962.34766 57951.44165 48817.26953 67081.99219 58517.49197 61871.625 69911.28171 72716.90967 80399.10156 43506.74609 EtherPE 18:1e_20:4 60897.03184 83558.80062 68217.79643 86245.55001 79416.41675 84890.66139 33592.06595 31464.14716 37558.64549 48826.87017 61169.49733 69192.42696 50021.0683 47054.59917 48664.86246 49519.86071 46822.01394 46121.2482 45538.62486 39722.64699 63285.10651 56979.89463 46608.77321 39841.26042 39656.45901 65699.45959 34166.83639 EtherPE 18:0e_20:4 48698.125 74152.375 59244.51292 67328.9375 65553.46797 67706.29795 18934.04102 16504.31836 23770.4668 28726.37695 35326.78428 38931.01879 34434.125 31942.0293 36120.12109 34844.00781 33438.1581 32854.31641 31972.73047 28231.02908 42677.56641 35031 32113.60261 25763.41702 24605.4318 37992.27344 22900.04102 SM d18:2_16:0 35523.375 45342.01069 50817.64453 45150.05859 38223.81462 45258.49229 20670.13867 17376.14648 23051.07813 23635.19727 34377.35056 29321.65625 31995.18234 30622.36914 34885.63862 34910.62891 34726.58594 32696.24887 32265.73421 28796.94644 38475.89063 36366.69345 31629.15444 32478.48047 26606.37109 41706.625 33071.90668 SM d18:1_16:0 164067.5418 193077.861 191022.1624 184695.8826 150973.3732 153195.1173 78594.92132 72899.85552 88605.17077 99581.53685 123002.1819 112697.0014 129029.9706 124721.6143 133729.7401 128372.4079 127008.9887 128191.4576 122534.4165 109696.7258 144208.2479 120624.916 118705.3738 93389.4124 94645.67116 114316.2241 107376.7063 PE 16:0_22:6 167528.2386 181696.6761 173389.2479 301824.7977 237595.2957 252666.6764 152683.301 123556.0234 195695.0588 206527.7502 244834.1959 203225.1656 201641.8449 183228.291 202753.8528 198006.4895 194523.8513 189021.1931 177598.1175 153003.0903 275137.3428 260365.9307 222612.0167 304332.1359 252904.3908 211454.7844 235342.7257 PE 18:1_20:4 107282.7222 101698.758 93676.34141 175465.5538 104121.6824 132006.088 81080.42181 61279.79308 116758.8356 116161.6869 138686.41 107185.8653 114238.4687 102464.8611 117377.8339 113782.0877 107353.4431 108960.5431 101431.5829 82065.02148 167977.7455 157949.7804 141737.6373 176792.9896 145575.096 123885.7284 124005.3234 PE 18:0_20:4 204447.5744 199748.7623 217120.0939 351025.7199 202205.0468 204015.534 54360.68674 48369.64539 102038.574 94919.59658 128673.0539 111451.8402 126025.5173 114145.3048 123202.268 121737.7498 122617.5846 115020.6616 107969.4591 94311.22653 160641.8036 125390.0284 106099.4054 127491.811 93731.48665 105391.9133 86523.43943 PE 20:0_18:2 14067.19434 15733.27874 14383.21974 16988.50195 15065.75195 16259.68164 5746.820801 4941.147949 8039.880859 6710.830078 7716.750488 8619.323242 9861.918945 9923.564453 10003.48438 8790.482976 9237.520508 10392.35156 9638.329102 8168.1875 9579.582846 8778.228516 7741.768066 8686.066406 7023.103516 9519.055664 7816.973145 EtherPE 18:2e_22:6 36378.51563 48434.24609 45678.23952 55647.09766 39574.82031 55584.78516 14622.80859 13585.2334 19207.42077 23401.37109 34338.42499 27364.34485 29024.60439 25035.88437 28836.01758 26689.04492 28861.73518 26817.26337 25876.44239 21159.60352 37173.48438 35411.05441 27482.32825 24200.42352 24536.42969 38491.9091 24477.24609 PG 18:0_18:2 38471.5979 48718.38672 42635.58537 64974.36328 46440.20925 57085.83065 9790.147461 8559.472935 17613.33398 12842.34809 20471.36523 21043.37285 24152.9826 21950.26595 24150.50953 24262.62695 24262.55424 22153.6549 21020.54883 16601.94903 27141.42582 24839.53906 16022.7518 28048.8725 14644.10913 24181.78516 13233.95117 EtherPE 18:1e_22:6 68265.47947 101778.3625 94991.62004 92247.52924 108093.0154 110601.254 49102.764 40412.67437 54352.95332 71830.69569 80097.0075 85196.64579 64865.06433 64156.77231 63649.30563 63051.62563 62056.83373 60276.35878 58423.12108 48955.59892 80676.70425 72634.96869 66037.50675 62502.57434 60117.56544 81204.59696 56703.89158 EtherPE 18:0e_22:6 53478.39908 84626.0625 78460.98438 73335.95266 85785.34375 91660.50422 38646.92188 34227.40497 50772.61719 59870.57422 63120.3353 72964.40482 55863.10774 51340.56641 53281.05078 53905.34375 50563.84375 49720.59375 50008.19574 43142.38439 71213.95313 60018.0963 59495.67809 50499.35547 52211.02344 61054.24979 44015.08215 PE 18:1_22:6 40810.36719 42298.30269 40291.1251 72254.97742 54517.57813 55580.22266 41193.18293 33711.80469 57488.05469 63034.98889 72649.26563 54381.57958 56928.82813 50858.83464 54604.02242 55216.41406 52931.17338 52041.08594 49390.15852 41792.75391 89856.74954 79325.56983 73379.2207 98104.10049 82028.84974 62719.83304 74794.88281 PC 15:0_18:2 5751.301773 6155.854492 7441.96875 7573.764102 8766.242188 8834.60036 12582.52197 7069.79877 8983.697413 10490.41113 12474.5564 11354.26799 9847.547906 9944.051758 10604.22042 10638.81506 11914.79696 10457.68077 9582.585938 8704.398438 11931.63386 13388.57129 13924.83691 16541.58984 13445.31034 15856.16654 13548.36523 PE 18:0_22:6 35822.658 38797.77185 47820.29162 79631.84884 56304.82113 48008.10827 14406.1921 14515.79124 30089.69486 26023.99908 37486.53752 33427.24669 33821.4445 29422.41075 31396.42603 29757.67406 31863.61047 29097.65693 27505.80274 23605.98455 44548.35316 35331.4251 28859.37256 43740.63143 28000.75245 28537.55199 29430.51021 PC 17:0_16:1 11788.95245 11568.48291 12649.24261 14023.8541 12871.12995 30184.39322 42410.49967 31759.59598 38921.28502 37433.28857 46019.15865 40778.4241 31188.00021 30358.90712 33356.36574 34290.42102 32869.95703 33625.42958 32730.28426 30690.91766 41848.39857 49394.523 47992.62518 58071.30548 38518.9578 55140.62019 40805.16978 PC 16:0_17:0 25676.82335 31668.20109 28699.61826 33163.29548 28240.9912 54963.63147 29105.29299 30262.58804 29735.79492 32821.10123 36088.83592 37290.28044 32909.10584 32349.09029 33872.93547 33253.91167 33850.60547 32781.23471 31414.09911 29078.72945 36343.10727 39755.49002 37873.32382 31117.83984 35599.36719 34577.63581 28878.63114 PC 17:0_18:2 995485.5543 1095980.304 1209581.559 1515455.24 1358010.566 1275226.548 742528.4591 624868.5595 893147.6875 934419.3263 963462.4367 1042608.428 957751.3961 877636.0224 974111.75 966789.3982 948166.227 962027.5625 886116.4375 810909.5625 930299.1875 899924.4375 868255.147 923107.0865 817465.7477 918852.9536 745807.193 PC 17:0_18:1 323021.3354 340722.3013 316880.6026 427409.504 360360.3372 382377.6564 420829.7421 379918.0877 466709.1444 499799.9376 536893.1004 483766.6226 455017.9131 430935.9037 474870.283 464325.8968 460450.728 460135.3474 439972.0224 400274.0915 636983.5321 605124.0468 544166.6276 587859.7312 474485.7779 673056.8771 494904.6235 PC 16:0_18:0 14709.96147 18183.51249 15959.76459 15071.57581 15013.37797 19645.85076 7870.26563 6696.429033 11002.84191 9276.224542 12288.77511 12209.59154 13340.70342 12823.15025 12515.77928 14090.28094 12074.28307 13638.89753 13066.27517 12014.22473 14607.33345 13803.80339 12806.00333 11143.54447 12057.21078 14672.93378 10170.9929 PC 18:2_18:3 19528.84766 20286.32227 21766.46875 26180.73438 23273.51225 19395.70867 6546.457031 4660.411133 12929.11621 8803.270508 7636.694824 11485.5127 11249.6709 10363.21875 10167.29575 10910.04402 11807.66992 10915.13839 10712.1875 8737.14874 8058.009766 7109.842773 7226.776367 11664.8623 6683.42252 6041.256836 5915.275879 EtherPC 16:0e_20:4 11648.50977 12927.88184 13037.91504 10993.43659 13465.68652 14494.49902 6609.605469 6758.369629 9318.667969 10792.22168 9248.010742 9901.744141 8914.787274 8555.474139 9524.180664 9498.320313 9190.298828 9599.508789 8652.804575 8877.513672 8844.895061 8909.214844 8488.231534 6959.037109 9103.916992 7917.202148 8364.84375 PC 18:0_18:2 15550.14147 17996.07879 21798.89258 18267.98488 20387.07665 21169.32227 12521.34277 9674.430664 15589.74414 14342.17662 12835.05371 12973.82715 13639.00879 14630.09766 14167.70479 15450.64453 13605.23047 13215.21234 11580.48892 11929.03613 10596.27637 10563.66211 12819.91797 11006.63281 10423.13867 9301.600005 9752.094072 PI 16:0_18:2 38171.44531 56618.53516 52698.21723 61686.56192 80182.5 73397.20494 61407.15625 46357.44357 70342.71094 90774.11719 64690 72273.03906 56381.88672 54606.5196 57726.40234 56848.68881 57700.21094 57433.90096 57042.3438 45852.72656 50366.79687 56836.91406 60747.60684 64770.33539 79466.74219 60208.84375 49955.01509 PI 16:0_18:1 11581.00579 18698.75828 15698.83477 17704.94242 21612.22925 22496.66563 18646.90007 14569.54266 16957.85861 21805.69438 19201.19228 19003.31791 17234.4558 15625.1332 16474.21126 16849.56012 16187.38549 16037.00023 15867.36856 13495.65884 14819.51668 16281.00251 16763.88497 18734.18503 19434.01537 18521.26757 13669.98773 PC 18:2_18:2 80525.12035 99560.73322 93862.02789 100472.6046 99495.9982 97068.44962 47945.22726 37459.6504 55117.71752 48524.80536 54284.68268 60421.03919 65250.88756 62926.09153 66888.69498 65772.14887 66326.29211 65133.22909 61743.45619 58500.75396 57565.43925 55133.2099 56417.25603 56969.17566 46978.24644 53454.8258 46666.48621 PC 19:0_18:2 880047.8766 1056945.354 957337.1065 1089531.434 908205.1443 1029675.887 322200.8607 269629.5834 447752.391 392500.6558 508826.1674 500358.5443 596876.5958 547108.0836 583616.4844 578591.7002 570605.4918 588788.8693 544424.5321 493567.7817 592105.6585 538102.7628 500547.2904 526185.8125 408461.7468 579255.3241 423117.4713 SM d18:1_22:0 67275.55163 73183.26754 92301.22315 106462.186 95589.671 89392.34536 26516.1058 23373.51371 39187.73205 40821.69531 50108.82934 44456.12815 57765.30183 53181.26483 53653.72646 59071.42371 53296.37083 54613.4228 51457.02605 45882.22063 61903.68638 50539.26577 52851.68999 44123.88196 42850.06747 50174.71921 51673.3328 PC 18:0_18:1 132616.2364 139792.533 121660.3764 141909.1944 122350.5325 141808.0615 79125.3016 63992.62713 98578.65625 84808.4993 113371.1625 98496.29637 110572.3113 111415.7221 121810.2365 111854.2373 113309.94 115633.9884 114906.8281 99124.91563 163238.8656 148231.9613 130167.4716 134664.6278 97361.00741 166855.563 111317.5608 PS 21:2_20:4 32132.0332 31573.58984 34892.13672 46957.22656 34427.59375 32638.2168 10457.69238 9657.875977 19027.94727 18067.53491 22707.83594 19906.82813 21943.88477 19966.40625 22751.69531 22748.11133 21420.29688 21502.89844 19754.50586 18655 26261.98828 22152.39258 19432.53586 22962.57031 18115.41016 19176.40039 16607.94922 PI 16:0_20:4 166122.1563 190618.6563 159332.5625 217344.0781 184591.875 217495.5156 212108.6875 157029.25 218047.7344 272898.375 261439.5938 223678.3906 217024.625 202714.7656 219078 221218.9844 214854.0156 214067.2656 213581.375 178763.6719 337772.5625 316156.8034 272205.7813 303533.0313 288722.375 314145.2813 223475.7656 PI 18:0_18:2 155035.7766 264115.4296 198938.7599 220165.8125 312505.4826 316057.4591 126077.2257 96787.82414 156239.9602 159582.8552 180983.7402 190529.1991 163488.134 152960.4807 171220.0017 169585.8268 166730.9815 171086.2152 158154.3633 126101.049 157101.1955 178200.7689 187971.127 183894.8115 215821.2537 198295.5568 137009.1213 PC 18:2_20:4 84702.88042 105591.511 93449.05134 84357.76188 80967.00329 108302.4888 34763.85781 28176.24735 43724.38506 43461.46158 54036.57704 46840.15749 62781.33309 60137.28987 65482.95016 65481.14462 62200.33311 63388.55152 62844.73274 55282.36891 70307.52036 66169.01963 60081.05591 56571.43086 52641.52716 63401.93699 58177.85723 PS 22:0_20:4 137372.717 147485.2802 121737.2388 129219.6243 93636.66651 139745.7727 74142.6902 67882.52823 80555.93335 87762.00439 112271.1504 85712.25855 110602.2355 106312.4101 116936.5291 111643.2507 110646.1874 111945.396 105077.1424 100463.4741 156538.1514 133069.5264 123448.96 101794.1265 104214.1719 140175.9736 110732.7417 PC 18:0_20:4 784549.9712 815531.6355 723325.898 856561.3352 447534.3231 686016.1692 133660.2657 129268.3038 194417.8197 208241.0598 310100.6035 225115.022 393031.5117 367129.572 405357.8538 397508.3319 403545.7537 382079.8615 364198.1864 330980.6278 514051.8101 409751.2209 313363.8359 275891.0736 256225.3351 430161.167 275424.2758 PC 18:0_20:3 123433.2651 101979.6944 117229.7429 164336.2899 61179.00329 83589.33477 42626.76062 38624.71245 49097.34894 48580.10547 80523.20722 59276.69531 83342.59981 77353.89746 86033.35706 82773.92775 85531.80469 82613.17118 80913.0927 74876.57813 138611.9836 107122.7638 87660.18239 85974.28422 61661.47583 117660.5746 72002.61104 PI 17:0_20:4 11738.86293 15020.8877 12821.62253 14390.94531 13085.37988 15210.20703 16334.31456 13402.70215 14325.58479 18399.74918 14950.10035 12258.68359 12987.40373 13156.12793 13173.72949 12656.09961 12474.88663 13117.26465 11723.80112 11128.49023 14566.51321 13922.08105 15275.75098 14137.86328 18541.16602 14075.91309 12986.25931 SM d42:2 68843.3089 72618.12254 59883.9729 77812.2607 59095.6351 72778.36702 61600.24253 58394.6522 65587.19559 72957.13172 80364.74902 67805.85702 64975.015 63865.81052 70445.53337 69001.29582 68937.49433 67311.86239 68279.75292 57523.45466 96377.48751 77061.49072 85811.94199 67047.22461 80123.9156 74052.86269 78117.32907 SM d18:1_24:0 16282.63547 18388.69969 17114.67046 22708.3475 25631.70506 24071.46098 16560.14467 14895.974 20224.03509 23739.99741 21119.21123 19929.97298 18596.6418 15728.04727 19119.70271 17226.89536 17134.03129 16853.43192 17785.95018 14350.37885 23445.11773 19668.61681 18802.33273 20769.35231 22940.75812 22894.54063 20733.60874 PI 16:0_22:6 12979.83105 17015.53711 15242.5459 17783.51367 18229.47656 23333.70898 19242.45117 15215.02734 16558.61133 21119.43945 23768.75391 20654.2832 17343.66992 16287.15137 18751.86523 18092.60156 19102.06641 18491.64063 17200.08594 14565.72266 24869.04883 24660.30664 21922.31641 25722.13672 24525.10742 25821.01563 18067.16211 PI 18:1_20:4 98253.16406 107406.1172 82640.67188 82589.86719 66238.95313 115350.3984 107596.8672 87455.625 75729.84375 97869.32813 131790.7969 72395.34375 106221.9141 100057.9297 111716.5313 106718.5938 108887.9453 104538.0938 103944.0469 89030.65625 169298.2288 154739.4531 144158.7656 139235.1719 193874.7656 178661.5469 146590.3281 PI 18:0_20:4 2389112.821 2732016.795 2445210.346 2705872.958 2163421.661 2738499.975 1242133.276 1118738.512 1347734.217 1706293.95 2240535.495 1817147.482 2027114.981 1909203.005 2037888.263 2011316.647 2045750.451 2029815.267 1963952.983 1765646.537 2741935.918 2653582.153 2299344.759 2160596.62 2201851.088 2669685.145 2076787.181 PI 18:0_20:3 245988.9152 287970.1989 272511.1078 523209.5091 134044.4861 272476.8899 101764.9463 86597.83627 98986.55917 139376.8993 210466.0155 143751.0368 209172.3397 183630.2513 197950.6587 192233.8874 195409.6815 190805.8202 183031.8553 149563.2206 387200.8823 347150.5881 275672.6288 294847.7819 260889.4013 429553.3033 222603.8463 PC 18:1_22:6 36081.62403 38471.85664 35983.52193 34348.08827 26011.85149 33002.47898 27391.50134 24925.7207 26154.85938 29221.76977 41220.14323 32004.02358 35456.03745 30964.33844 34454.04177 35263.15708 32384.10399 33085.66084 31995.56069 31116.18319 56308.73221 46698.15024 43385.72007 33292.80197 33319.38791 48048.02022 38839.78243 PC 18:0_22:6 139243.6334 150427.8244 146687.1876 181358.575 110237.1345 133187.9728 32675.84717 33324.21582 48478.14907 52178.62377 80273.4939 59593.90535 85161.45171 80187.8348 87199.94017 86383.25145 82205.64923 82086.41196 78951.23888 70771.97499 139081.9998 104471.1123 78710.6591 73485.74622 56128.16902 105143.9418 66649.7114 PI 18:0_22:6 29027.58789 40206.49609 37475.36328 39037.51563 39174.10156 49316.12891 36296.91797 33367.62891 30857.44727 38158.00391 50274.20313 46012.42969 40512.17969 38920.59766 41359.4375 41327.48438 42520.55859 41894.47656 39091.90234 35844.73828 51207.22266 58520.05859 56560.20703 61201.39063 63067.38672 63285.66406 49359.95313 PC 20:4_22:6 9980.855949 12493.42093 11667.51579 8401.094192 8603.605254 14249.13913 9414.289625 7940.767668 7798.355154 8269.857883 12601.7486 9731.456061 12425.55425 12103.70538 11728.16483 12658.71102 13628.32617 11647.6938 12662.37962 10924.5176 20171.26654 21942.19249 18582.9321 16435.24381 16660.6644 20584.34315 17498.72012 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Standardized name mz RT REFMET_ID FAHFA 2:0_18:3 - 360.2288 2.79 - FAHFA 2:0_20:4 - 451.2705 1.26 - LPE 16:0 LPE 16:0 475.27 1.05 RM0134456 LPE 18:2 LPE 18:2 479.3018 1.98 RM0048672 LPE 18:0 LPE 18:0 499.2758 1.07 RM0017276 LPE 20:4 LPE 20:4 528.4156 2.43 RM0097815 FAHFA 16:1_18:3 - 532.4471 3.03 - FAHFA 16:0_18:2 - 553.3395 1.19 - LPC 16:0/0:0 LPC 16:0/0:0 577.3391 1.06 RM0135071 LPC 18:2/0:0 LPC 18:2/0:0 579.3545 1.35 RM0134486 LPC 18:1/0:0 LPC 18:1/0:0 580.4469 2.79 RM0048632 FAHFA 18:2_20:4 - 584.4785 3.22 - FAHFA 18:1_20:3 - 595.5179 5.77 - Cer_NS d18:1_16:0 Cer 18:1;O2/16:0 597.5325 6.02 RM0135485 Cer_NDS d18:0_16:0 Cer 18:0;O2/16:0 601.3388 1.07 RM0135506 LPC 20:4/0:0 LPC 20:4/0:0 609.4005 2.81 RM0048623 LPC 20:0/0:0 LPC 20:0/0:0 619.5904 7.86 RM0134479 LPC 22:6/0:0 LPC 22:6/0:0 637.6007 7.48 RM0134489 Cer_NP t18:0_22:0 Cer 18:0;O3/22:0 645.6056 7.94 RM0135528 Cer_NS d18:1_20:0 Cer 18:1;O2/20:0 651.6158 7.82 RM0135487 Cer_NS d18:1_22:0 Cer 18:1;O2/22:0 693.6273 8.19 RM0135488 Cer_NS d18:1_23:0 Cer 18:1;O2/23:0 697.6216 7.48 RM0138865 Cer_NS d18:2_24:1 Cer 18:2;O2/24:1 705.6275 7.93 RM0134208 Cer_NS d18:1_24:1 Cer 18:1;O2/24:1 707.6429 8.5 RM0134169 Cer_NS d18:1_24:0 Cer 18:1;O2/24:0 711.637 7.81 RM0135489 Cer_NP t18:0_23:0 Cer 18:0;O3/23:0 713.5 5.32 RM0121957 PE 16:0_18:2 PE 16:0_18:2 721.505 5.75 RM0011470 EtherPE 16:1e_20:4 PE O-16:1/20:4 723.6371 7.56 RM0054520 Cer_NP t18:0_24:1 Cer 18:0;O3/24:1 725.5364 6.38 RM0041332 EtherPE 18:1e_18:2 PE O-18:1/18:2 725.653 8.13 RM0054646 Cer_NP t18:0_24:0 Cer 18:0;O3/24:0 727.551 6.43 RM0135524 EtherPE 18:0e_18:2 PE O-18:0/18:2 737.5 5.38 RM0104525 PE 16:0_20:4 PE 16:0_20:4 739.5136 5.5 RM0134803 PE 18:1_18:2 PE 18:1_18:2 741.5313 5.99 RM0011593 PE 18:0_18:2 PE 18:0_18:2 741.5311 5.13 RM0001471 EtherPE 16:1e_22:6 PE O-16:1/22:6 746.5141 4.59 RM0134799 PG 16:0_18:1 PG 16:0_18:1 746.5554 4.3 RM0097814 SM d17:1_16:0 SM 17:1;O2/16:0 747.5193 5.79 RM0060201 EtherPE 18:2e_20:4 PE O-18:2/20:4 749.5362 6.43 RM0098404 EtherPE 18:1e_20:4 PE O-18:1/20:4 751.5505 6.49 RM0008857 EtherPE 18:0e_20:4 PE O-18:0/20:4 758.5576 4.2 RM0017815 SM d18:2_16:0 SM 18:2;O2/16:0 760.5737 4.58 RM0135573 SM d18:1_16:0 SM 18:1;O2/16:0 761.5003 5.36 RM0135543 PE 16:0_22:6 PE 16:0_22:6 763.5157 5.55 RM0104542 PE 18:1_20:4 PE 18:1_20:4 765.5315 6.05 RM0001489 PE 18:0_20:4 PE 18:0_20:4 769.5629 5.8 RM0134782 PE 20:0_18:2 PE 18:2_20:0 771.5221 5.86 RM0001998 EtherPE 18:2e_22:6 PE O-18:2/22:6 772.5258 4.82 RM0054704 PG 18:0_18:2 PG 18:0_18:2 773.5363 6.39 RM0011341 EtherPE 18:1e_22:6 PE O-18:1/22:6 775.5511 6.46 RM0054678 EtherPE 18:0e_22:6 PE O-18:0/22:6 787.5158 5.53 RM0054394 PE 18:1_22:6 PE 18:1_22:6 787.5361 4.52 RM0043843 PC 15:0_18:2 PC 15:0_18:2 789.531 6.03 RM0011315 PE 18:0_22:6 PE 18:0_22:6 789.5522 4.92 RM0001469 PC 17:0_16:1 PC 16:1_17:0 791.5664 5.34 RM0103485 PC 16:0_17:0 PC 16:0_17:0 815.5693 5.14 RM0000552 PC 17:0_18:2 PC 17:0_18:2 817.5847 5.53 RM0000392 PC 17:0_18:1 PC 17:0_18:1 819.5967 6.01 RM0090135 PC 16:0_18:0 PC 16:0_18:0 823.5359 5.99 RM0000437 PC 18:2_18:3 PC 18:2_18:3 825.5877 5.62 RM0171045 EtherPC 16:0e_20:4 PC O-16:0/20:4 829.5828 5.46 RM0053653 PC 18:0_18:2 PC 18:0_18:2 832.5107 4.08 RM0097845 PI 16:0_18:2 PI 16:0_18:2 834.5263 4.39 RM0056506 PI 16:0_18:1 PI 16:0_18:1 839.5684 4.94 RM0134531 PC 18:2_18:2 PC 18:2/18:2 843.6004 5.81 RM0134908 PC 19:0_18:2 PC 18:2_19:0 844.6668 6.61 RM0000021 SM d18:1_22:0 SM 18:1;O2/22:0 845.6151 6.21 RM0138870 PC 18:0_18:1 PC 18:0_18:1 847.5366 6.06 RM0171088 PS 21:2_20:4 PS 20:4_21:2 856.5112 4.14 RM0162336 PI 16:0_20:4 PI 16:0_20:4 860.5426 4.61 RM0138712 PI 18:0_18:2 PI 18:0_18:2 863.5674 4.98 RM0106274 PC 18:2_20:4 PC 18:2_20:4 865.5833 5.36 RM0171068 PS 22:0_20:4 PS 20:4_22:0 867.6004 5.87 RM0058261 PC 18:0_20:4 PC 18:0_20:4 869.617 6.09 RM0134946 PC 18:0_20:3 PC 18:0_20:3 870.5272 4.4 RM0170562 PI 17:0_20:4 PI 17:0_20:4 870.6828 6.68 RM0056535 SM d42:2 SM 42:2;O2 872.6978 7.31 RM0122625 SM d18:1_24:0 SM 18:1;O2/24:0 880.5108 4.13 RM0060142 PI 16:0_22:6 PI 16:0_22:6 882.5265 4.27 RM0056502 PI 18:1_20:4 PI 18:1_20:4 884.5436 4.67 RM0057263 PI 18:0_20:4 PI 18:0_20:4 886.5559 4.83 RM0134537 PI 18:0_20:3 PI 18:0_20:3 889.5834 5.35 RM0106376 PC 18:1_22:6 PC 18:1_22:6 891.5995 5.85 RM0036601 PC 18:0_22:6 PC 18:0_22:6 908.5421 4.66 RM0134875 PI 18:0_22:6 PI 18:0_22:6 911.5659 4.98 RM0027240 PC 20:4_22:6 PC 20:4_22:6 -2.0146 RM0000954 METABOLITES_END #END