#METABOLOMICS WORKBENCH hectorp_20230306_152042 DATATRACK_ID:3778 STUDY_ID:ST002503 ANALYSIS_ID:AN004112 PROJECT_ID:PR001617 VERSION 1 CREATED_ON March 9, 2023, 5:33 pm #PROJECT PR:PROJECT_TITLE Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid PR:PROJECT_TITLE Delivery to Tissues and Circulating Fatty Acid Levels PR:PROJECT_TYPE MS quantitative analysis PR:PROJECT_SUMMARY Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we PR:PROJECT_SUMMARY visualized FA transfer by ECs using click chemistry. Apical FA interaction with PR:PROJECT_SUMMARY EC CD36 induces actin reorganization, caveolin-1 tyrosine 14 (Cav-1Y14) PR:PROJECT_SUMMARY phosphorylation, and ceramide generation in caveolae, culminating in caveolae PR:PROJECT_SUMMARY internalization into FA/CD36/ceramide vesicles that are secreted basolaterally PR:PROJECT_SUMMARY as small extracellular vesicles, sEVs (exosomes). In transwells, ECs expressing PR:PROJECT_SUMMARY fluorescent CD63 (exosomal marker) transfer FAs to underlying myotubes in PR:PROJECT_SUMMARY CD63-labeled sEVs. In vivo FA-CD63-CD36 transfer from ECs to muscle is shown PR:PROJECT_SUMMARY using a mouse with EC-specific expression of emGFP-CD63. CD36 depletion, PR:PROJECT_SUMMARY actin-binding latrunculin-B, Src inhibition, Cav-1Y14 mutation, and membrane PR:PROJECT_SUMMARY neutral sphingomyelinase inhibition by GW4869 helped map the FA-sEV pathway. PR:PROJECT_SUMMARY Injecting GW4869 to mice reduced muscle FA uptake, raised plasma FAs and lowered PR:PROJECT_SUMMARY glucose, mimicking prominent Cd36-/- phenotypes. The FA-sEV pathway we describe PR:PROJECT_SUMMARY contributes to crosstalk between ECs and underlying cells and links regulation PR:PROJECT_SUMMARY of membrane ceramide to blood FAs. PR:INSTITUTE Washington University in St. Louis PR:DEPARTMENT IM-Nutitrional Science PR:LABORATORY Abumrad Lab PR:LAST_NAME Palacios PR:FIRST_NAME Hector PR:ADDRESS West Building 00201, St. Louis, Missouri, 63110, USA PR:EMAIL hectorp@wustl.edu PR:PHONE 314-362-5397 #STUDY ST:STUDY_TITLE Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid ST:STUDY_TITLE Delivery to Tissues and Circulating Fatty Acid Levels ST:STUDY_TYPE Membrane ceramide and Fatty Acid Uptake ST:STUDY_SUMMARY Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we ST:STUDY_SUMMARY visualized FA transfer by ECs using click chemistry. Apical FA interaction with ST:STUDY_SUMMARY EC CD36 induces actin reorganization, caveolin-1 tyrosine 14 (Cav-1Y14) ST:STUDY_SUMMARY phosphorylation, and ceramide generation in caveolae, culminating in caveolae ST:STUDY_SUMMARY internalization into FA/CD36/ceramide vesicles that are secreted basolaterally ST:STUDY_SUMMARY as small extracellular vesicles, sEVs (exosomes). In transwells, ECs expressing ST:STUDY_SUMMARY fluorescent CD63 (exosomal marker) transfer FAs to underlying myotubes in ST:STUDY_SUMMARY CD63-labeled sEVs. In vivo FA-CD63-CD36 transfer from ECs to muscle is shown ST:STUDY_SUMMARY using a mouse with EC-specific expression of emGFP-CD63. CD36 depletion, ST:STUDY_SUMMARY actin-binding latrunculin-B, Src inhibition, Cav-1Y14 mutation, and membrane ST:STUDY_SUMMARY neutral sphingomyelinase inhibition by GW4869 helped map the FA-sEV pathway. ST:STUDY_SUMMARY Injecting GW4869 to mice reduced muscle FA uptake, raised plasma FAs and lowered ST:STUDY_SUMMARY glucose, mimicking prominent Cd36-/- phenotypes. The FA-sEV pathway we describe ST:STUDY_SUMMARY contributes to crosstalk between ECs and underlying cells and links regulation ST:STUDY_SUMMARY of membrane ceramide to blood FAs. ST:INSTITUTE Washington University in St. Louis ST:DEPARTMENT IM-Nutitrional Science ST:LABORATORY Abumrad Lab ST:LAST_NAME Palacios ST:FIRST_NAME Hector ST:ADDRESS West Building 00201, St. Louis, Missouri, 63110, USA ST:EMAIL hectorp@wustl.edu ST:PHONE 314-362-5397 #SUBJECT SU:SUBJECT_TYPE Cultured cells 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 5 KO1n_05 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1n_05.mzML SUBJECT_SAMPLE_FACTORS 13 KO1n_13 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1n_13.mzML SUBJECT_SAMPLE_FACTORS 21 KO1n_21 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1n_21.mzML SUBJECT_SAMPLE_FACTORS 7 KO1p_07 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1p_07.mzML SUBJECT_SAMPLE_FACTORS 15 KO1p_15 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1p_15.mzML SUBJECT_SAMPLE_FACTORS 23 KO1p_23 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO1p_23.mzML SUBJECT_SAMPLE_FACTORS 6 KO3n_06 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3n_06.mzML SUBJECT_SAMPLE_FACTORS 14 KO3n_14 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3n_14.mzML SUBJECT_SAMPLE_FACTORS 22 KO3n_22 Genotype:Knock-out | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3n_22.mzML SUBJECT_SAMPLE_FACTORS 8 KO3p_08 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3p_08.mzML SUBJECT_SAMPLE_FACTORS 16 KO3p_16 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3p_16.mzML SUBJECT_SAMPLE_FACTORS 24 KO3p_24 Genotype:Knock-out | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_KO3p_24.mzML SUBJECT_SAMPLE_FACTORS 1 WT1n_01 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1n_01.mzML SUBJECT_SAMPLE_FACTORS 9 WT1n_09 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1n_09.mzML SUBJECT_SAMPLE_FACTORS 17 WT1n_17 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1n_17.mzML SUBJECT_SAMPLE_FACTORS 3 WT1p_03 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1p_03.mzML SUBJECT_SAMPLE_FACTORS 11 WT1p_11 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1p_11.mzML SUBJECT_SAMPLE_FACTORS 19 WT1p_19 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT1p_19.mzML SUBJECT_SAMPLE_FACTORS 2 WT3n_02 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3n_02.mzML SUBJECT_SAMPLE_FACTORS 10 WT3n_10 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3n_10.mzML SUBJECT_SAMPLE_FACTORS 18 WT3n_18 Genotype:Wild-type | Treatment:Neg Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3n_18.mzML SUBJECT_SAMPLE_FACTORS 4 WT3p_04 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3p_04.mzML SUBJECT_SAMPLE_FACTORS 12 WT3p_12 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3p_12.mzML SUBJECT_SAMPLE_FACTORS 20 WT3p_20 Genotype:Wild-type | Treatment:Pos Batch=1a; RAW_FILE_NAME=HSS_Nada_Exo_Pos_IPA_WT3p_20.mzML SUBJECT_SAMPLE_FACTORS 1 WT1n_01_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_01.mzML SUBJECT_SAMPLE_FACTORS 2 WT3n_02_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_02.mzML SUBJECT_SAMPLE_FACTORS 3 WT1p_03_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_03.mzML SUBJECT_SAMPLE_FACTORS 4 WT3p_04_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_04.mzML SUBJECT_SAMPLE_FACTORS 5 KO1n_05_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_05.mzML SUBJECT_SAMPLE_FACTORS 6 KO3n_06_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_06.mzML SUBJECT_SAMPLE_FACTORS 7 KO1p_07_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_07.mzML SUBJECT_SAMPLE_FACTORS 8 KO3p_08_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_08.mzML SUBJECT_SAMPLE_FACTORS 9 WT1n_09_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_09.mzML SUBJECT_SAMPLE_FACTORS 10 WT3n_10_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_10.mzML SUBJECT_SAMPLE_FACTORS 11 WT1p_11_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_11.mzML SUBJECT_SAMPLE_FACTORS 12 WT3p_12_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_12.mzML SUBJECT_SAMPLE_FACTORS 13 KO1n_13_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_13.mzML SUBJECT_SAMPLE_FACTORS 14 KO3n_14_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_14.mzML SUBJECT_SAMPLE_FACTORS 15 KO1p_15_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_15.mzML SUBJECT_SAMPLE_FACTORS 16 KO3p_16_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_16.mzML SUBJECT_SAMPLE_FACTORS 17 WT1n_17_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_17.mzML SUBJECT_SAMPLE_FACTORS 18 WT3n_18_FA Genotype:Wild-type | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_18.mzML SUBJECT_SAMPLE_FACTORS 19 WT1p_19_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_19.mzML SUBJECT_SAMPLE_FACTORS 20 WT3p_20_FA Genotype:Wild-type | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_20.mzML SUBJECT_SAMPLE_FACTORS 21 KO1n_21_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_21.mzML SUBJECT_SAMPLE_FACTORS 22 KO3n_22_FA Genotype:Knock-out | Treatment:Neg Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_22.mzML SUBJECT_SAMPLE_FACTORS 23 KO1p_23_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_23.mzML SUBJECT_SAMPLE_FACTORS 24 KO3p_24_FA Genotype:Knock-out | Treatment:Pos Batch=1b; RAW_FILE_NAME=Nada_iHILIC_Exosomes_221_PNS_24.mzML #COLLECTION CO:COLLECTION_SUMMARY Samples were collected and aliquots representing the same EV counts were dried CO:COLLECTION_SUMMARY under nitrogen, and resuspended in 2:2:1 acetonitrile:methanol:H2O (v/v) (for CO:COLLECTION_SUMMARY polar metabolites, eg. fatty acids, phospholipids) or in 100% isopropanol (for CO:COLLECTION_SUMMARY less-polar metabolites, eg. ceramides). The samples were mixed on an orbital CO:COLLECTION_SUMMARY shaker (360 rpm) for 1 min at room temperature before the LC/MS analysis. CO:SAMPLE_TYPE Cultured cells #TREATMENT TR:TREATMENT_SUMMARY Myotube Treatment with hMEC Generated FA-sEV: hMECs grown to confluence were TR:TREATMENT_SUMMARY serum-starved and treated with OA:BSA (100µM:50µM) or BSA (50µM controls). TR:TREATMENT_SUMMARY The sEVs were isolated from media collected over 48h and particle number and TR:TREATMENT_SUMMARY protein content determined. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Samples were collected and aliquots representing the same EV counts were dried SP:SAMPLEPREP_SUMMARY under nitrogen, and resuspended in 2:2:1 acetonitrile:methanol:H2O (v/v) (for SP:SAMPLEPREP_SUMMARY polar metabolites, eg. fatty acids, phospholipids) or in 100% isopropanol (for SP:SAMPLEPREP_SUMMARY less-polar metabolites, eg. ceramides). The samples were mixed on an orbital SP:SAMPLEPREP_SUMMARY shaker (360 rpm) for 1 min at room temperature before the LC/MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Waters CORTECS UPLC C18 (150 x 2.1mm,1.6um) CH:SOLVENT_A A: 60% acetonitrile, 40% water, 0.1% formic acid, 10 mM ammonium formate, 2.5 mM CH:SOLVENT_A medronic acid CH:SOLVENT_B 90% 2-propanol, 10% acetonitrile, 0.1% formic acid, 10 mM ammonium formate CH:FLOW_GRADIENT 0-2 min, 30% B; 17 min, 75% B; 20 min, 85% B; 23-26 min, 100% B; 26 min, 30% B CH:FLOW_GRADIENT followed by a re-equilibration phase of 5 min. CH:FLOW_RATE .25ml/min CH:COLUMN_TEMPERATURE 60 CH:METHODS_FILENAME LC_Method.pdf #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE MS_Method.pdf #MS MS:INSTRUMENT_NAME Agilent 6545 QTOF MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS - #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak Area MS_METABOLITE_DATA_START Samples WT1n_09 WT3n_18 WT1p_19 WT3p_12 KO1n_13 KO3n_14 KO1p_15 KO3p_16 WT1n_01 WT3n_10 WT1p_11 WT3p_20 KO1n_05 KO3n_06 KO1p_07 KO3p_08 Factors Genotype:Wild-type | Treatment:Neg Genotype:Wild-type | Treatment:Neg Genotype:Wild-type | Treatment:Pos Genotype:Wild-type | Treatment:Pos Genotype:Knock-out | Treatment:Neg Genotype:Knock-out | Treatment:Neg Genotype:Knock-out | Treatment:Pos Genotype:Knock-out | Treatment:Pos Genotype:Wild-type | Treatment:Neg Genotype:Wild-type | Treatment:Neg Genotype:Wild-type | Treatment:Pos Genotype:Wild-type | Treatment:Pos Genotype:Knock-out | Treatment:Neg Genotype:Knock-out | Treatment:Neg Genotype:Knock-out | Treatment:Pos Genotype:Knock-out | Treatment:Pos Cer_NS d18:1_16:0 436683 397224 340366 492913 244860 283941 213093 335666 816677 860526 601445 766225 651517 223202 346193 278528 Cer_NS d18:1_24:0 150433 168294 192996 141969 220404 181244 239389 168299 187799 217493 151574 161633 157679 155507 138784 167710 Cer_NS d18:1_24:1 247450 188562 206361 254442 118290 183673 136795 130475 576809 529388 366819 591854 159822 102759 118092 122657 Cer_NS d42:3 74072 72789 102351 107438 27209 34177 28912 54203 237374 162916 139817 221282 120199 31263 52395 72284 DG 16:0_18:1 377462 713295 627262 407668 285496 339213 415152 263691 170210 304418 541221 446983 274234 284739 123593 288215 HexCer_NS d18:1_16:0 993997 1115497 1269004 1385576 147880 144450 150161 173064 4380316 2006214 1688524 2326625 1077042 169173 683420 317836 HexCer_NS d18:1_22:0 569006 652772 767227 656451 578411 815366 585326 803997 666309 538052 609627 602512 523966 508921 479968 597695 LPC 0:0/16:0 465058 1670035 724748 993780 361605 564330 398972 251320 8860413 1645537 1379905 9414150 1675615 802771 1170939 996286 LPC 0:0/18:0 780994 1718635 638180 936839 438047 880436 603604 325806 7585071 1561666 1396212 8843053 1557168 1088114 1102683 1197586 LPC 0:0/18:1 33558 187857 126062 194526 31096 61730 60025 39562 1217638 286582 225421 1393391 362425 134620 228660 160830 LPC 0:0/18:2 31354 95827 104387 88687 30415 54341 38008 69670 656066 151974 84341 129877 505811 68926 339135 81589 LPC 15:0/0:0 33808 109316 94069 147134 31506 18661 12911 35611 1961295 460986 464623 476912 881795 141316 603121 463956 LPC 16:0/0:0 5586410 15389893 14205493 15897269 4348544 3111693 2836974 3447083 158133888 40865940 37550256 47241412 54355848 10809844 31527044 29531460 LPC 18:0/0:0 7364680 15503779 12233129 16760151 4854763 3922719 4028050 4058032 164865968 38071324 42958016 46563392 46962072 11983067 29295962 32977320 LPC 18:1/0:0 33558 187857 126062 194526 31096 61730 60025 39562 1217638 286582 225421 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172706 133524 192910 282543 140917 159964 216382 PS 36:1 431423 373028 564141 766462 271499 351028 326197 485967 474639 406404 502250 713811 336528 366700 341818 535815 PS 36:2 110749 99120 121027 163374 119923 89233 111979 102937 79921 77368 66306 89327 115878 52254 67856 71188 SM d16:1_16:0 2828765 3856090 3643788 4363657 1934604 3720982 1860241 3690171 11467824 5706941 5959466 6877373 13462889 5139440 6847944 8955154 SM d18:1_18:0 4206353 8030650 7241890 8428781 3860223 8337180 3594059 8807386 10279403 7134075 4701735 7663265 9740687 5885361 6090128 6554150 SM d32:1 327772 324626 336395 193959 123510 68840 213594 137527 65146 92273 113803 81213 86889 60894 60148 64960 SM d33:1 607411 977939 406157 445102 289094 1116609 606247 608692 594405 291008 183300 1250769 677243 488062 418900 323829 SM d34:0 1646120 2962621 2787042 3265476 2208196 3136009 1871952 3416860 5208840 2996227 2254000 3327591 7453461 2501997 4332387 3348925 SM d34:1 12769087 29060834 9334163 12277851 7131820 41747648 15365928 20573728 38907924 10547949 5298799 47473576 41743064 15232625 16590565 10971247 SM d34:2 8049612 11850088 10575272 11903473 4874319 9538158 4698269 9549478 42358380 23229106 21210754 25707662 49024200 19767890 25155390 33708028 SM d35:1 735624 1363277 1260417 1510789 661872 1353385 643248 1580530 1983699 1363329 924500 1479116 2398672 1168261 1479840 1524488 SM d36:0 107105 265132 235031 253694 104043 268398 112632 288418 207942 183532 118039 202275 179615 128494 133767 130671 SM d36:2 2144161 3747069 3658924 3988961 1632395 3485079 1565978 4053834 6508566 4373964 3530752 4477331 8942370 3841674 4193624 6309973 SM d37:1 123165 277905 257363 324438 129677 296273 118277 339471 324778 230178 154554 266202 282618 166917 190551 179788 SM d38:0 148748 305478 254181 341914 148131 367253 145140 341774 208173 189578 112572 172690 172301 109032 124092 106488 SM d38:1 1269041 2191962 2084181 2538797 1153866 2383820 1072449 2669912 2548411 1864984 1280525 1975627 2133870 1454095 1514878 1533337 SM d38:2 422548 681562 703512 826687 343130 740005 304191 729497 1812489 954571 634169 987093 2376207 751699 890670 1037188 SM d39:1 457986 931494 789769 1029185 424867 1004572 415189 1028683 918950 675516 438434 728210 774002 517241 574209 573946 SM d40:1 3347410 5550358 4560916 6419327 3019237 6586513 3010625 6175654 5617875 4958415 3026859 4606366 4427084 3332264 3549529 3088007 SM d40:2 1672607 3249246 3070957 3400861 1497897 3072879 1482956 3658962 5122756 3633204 2405230 3390754 5861380 2667492 3109132 3902468 SM d41:1 587190 1018006 861349 1185314 550575 1240421 560709 1137833 1000334 840266 497021 871063 793626 494036 623771 538062 SM d41:2 1132504 2059666 1880521 2237446 1040804 2113825 966952 2149037 2915412 2140341 1591172 2168934 2828381 1583070 1812494 2040466 SM d41:3 232695 428919 399202 459415 175771 367968 146535 428620 827017 529916 406262 519405 1085694 404626 470034 600225 SM d42:1 1422475 1779697 1669958 2312405 1309910 2662929 1361194 2284106 2670528 2183393 1147909 2059298 1824718 1099849 1452487 1196481 SM d42:2 9006153 14222412 14721452 17359708 8134171 14353047 7640065 17183276 27440268 19287034 18553932 23401182 24540606 14689785 19952310 20979660 SM d42:3 4684830 7615952 7503842 8071099 4096581 6510582 3741849 7968486 21003392 13216241 10996971 14490475 24357022 9845185 14091346 17634116 TG 14:0_16:0_18:1 3299687 1518661 3057465 1488498 1925221 3483948 3357466 3228572 3132945 1255260 1436896 3411491 1567022 1437613 1518981 3258610 TG 15:0_16:0_18:1 2142759 1018822 2541981 1104370 1412204 2292433 2537854 2403154 2424536 1245864 1083613 2301682 1266863 1328154 1116221 2287124 TG 16:0_16:0_17:0 2073912 903548 2017791 894049 1437292 1991221 2177476 2065195 2109368 975454 1241646 1981224 959804 1107615 1015621 1927251 TG 16:0_16:0_18:1 2046875 959001 2238027 799737 1346055 2049017 2504433 2074828 2428861 1098868 984008 2166287 1010623 1285690 1251024 2269456 TG 16:0_16:1_18:1 2971747 1438517 2749682 1070346 1837992 2708802 2769476 2992718 3058482 1132849 1330879 2798029 1344861 1464986 1248083 2871747 TG 16:0_16:1_18:2 1565367 617832 1411162 644299 974899 1504065 1436382 1616892 1466058 619950 772719 1594271 778703 702597 718098 1417778 TG 16:0_17:0_18:0 1899791 874101 1661816 794286 968683 1720150 1734784 1594978 1488504 808888 995914 1503798 1005275 919508 1046119 1556042 TG 16:0_17:0_18:1 1555342 791703 1569180 860578 1013791 1494543 1529048 1557578 1624640 852984 844197 1589955 729558 829090 926930 1589080 TG 16:0_17:1_18:1 1520780 544199 1285678 693831 960234 1271046 1364315 1267565 1280401 711810 574449 1334609 540535 589218 694159 1628802 TG 16:0_18:0_18:1 1357464 788478 1455178 689512 958163 1562772 1418734 1542824 1658492 887077 652614 1536744 953861 738702 782213 1383163 TG 16:0_18:0_20:0 380523 220305 368289 248836 270969 355210 366989 399651 400174 253357 319459 337549 304512 297658 212672 332773 TG 16:0_18:1_18:1 2061885 948574 1848133 910592 1325217 2084122 1999287 2190513 1955988 976076 1049296 1972199 889567 932502 1068388 1853502 TG 16:0_18:1_18:2 1897937 988878 2049581 816332 1167528 1865506 1990163 1817376 1908868 844584 900032 1854646 943952 833671 916574 1904552 TG 16:0_18:1_20:4 880905 362754 876801 416169 641987 901443 874699 928299 842649 407053 380096 871855 394930 407412 381407 856301 TG 16:0_18:2_18:2 876191 381292 898250 354248 562937 863773 821343 840475 918558 424829 390074 852119 381291 407715 353638 805369 TG 17:0_18:1_18:1 1236463 529775 1130617 493135 711344 1206696 1167145 1217942 1158654 503200 625187 1106281 464739 676141 653008 1120388 TG 18:0_18:0_18:1 472603 250137 483763 239721 249128 419453 376430 456081 410674 294802 242132 468977 319563 297620 290661 432958 TG 18:0_18:1_18:1 1299679 826780 1384691 793364 816463 1451027 1435319 1488696 1443358 762897 823541 1408792 783346 842263 798444 1422036 TG 18:0_18:1_20:4 632843 296535 608912 307219 468213 644937 616925 633214 617176 277332 274468 615561 307345 304281 296676 588808 TG 18:2_18:2_18:2 676398 346661 695872 326905 526203 715452 696418 687074 692474 327883 274342 696250 303864 309158 321315 666389 TG 18:2_18:2_18:3 167757 96254 146746 93574 116647 156419 159134 160568 164395 71403 80269 143532 63716 72867 85355 154927 TG 46:1 457667 158642 379945 169260 285363 438287 484931 377943 576284 166646 160760 422335 153528 88308 216363 462709 TG 46:2 1132494 510099 913279 617025 1035750 1090342 839264 1075605 1002704 447500 538006 1067892 603184 548153 519953 1243684 TG 47:1 1993462 1004824 2177463 960929 1424819 1956279 2143102 2107852 2124756 993506 819398 2049292 987910 1000738 1027230 2086245 TG 48:1 1037694 371415 1022049 344123 529973 834984 940998 993769 1017094 358717 357549 993545 375753 372063 362365 1023204 TG 48:2 2825129 1145789 2518311 1169563 1806761 2964871 2587670 2602715 2648387 1385052 1167245 2521623 1204640 1214334 1289254 2582681 TG 49:1 2669502 986409 2407799 1278010 1344714 2398024 2248924 2527472 2344005 1031255 1018019 2314450 1184427 1327303 1082305 2319478 TG 49:2 1807054 810103 1930115 821674 1295740 2141346 1906938 1808586 1860297 943998 925022 1985203 836397 842656 925424 1875576 TG 50:2 880671 313944 864905 298097 497637 704790 893026 815560 886167 309311 327551 784595 321088 314047 350191 825201 TG 54:5 235252 74036 254147 91674 163622 242182 236022 258670 259555 95980 73945 224617 93269 80929 79394 247107 TG 56:3 996543 499102 986742 473503 626211 1007456 961412 937260 948179 504930 421225 922360 500177 537686 532300 910256 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Cer_NS d18:1_16:0 Cer_NS d18:1_24:0 Cer_NS d18:1_24:1 Cer_NS d42:3 DG 16:0_18:1 HexCer_NS d18:1_16:0 HexCer_NS d18:1_22:0 LPC 0:0/16:0 LPC 0:0/18:0 LPC 0:0/18:1 LPC 0:0/18:2 LPC 15:0/0:0 LPC 16:0/0:0 LPC 18:0/0:0 LPC 18:1/0:0 PC 14:0_16:0 PC 15:0_16:0 PC 15:0_18:2 PC 15:0_20:4 PC 16:0_16:0 PC 16:0_16:1 PC 16:0_17:0 PC 16:0_17:1 PC 16:0_18:0 PC 16:0_18:1 PC 16:0_18:2 PC 16:0_18:3 PC 16:0_20:3 PC 16:0_20:4 PC 16:0_22:4 PC 16:0_22:5 PC 16:0_22:6 PC 16:1_18:1 PC 17:0_18:1 PC 17:0_20:3 PC 18:0_18:1 PC 18:0_18:2 PC 18:0_20:2 PC 18:0_20:3 PC 18:0_20:4 PC 18:0_20:5 PC 18:0_22:4 PC 18:0_22:5 PC 18:0_22:6 PC 18:1_18:1 PC 18:1_18:2 PC 18:1_20:3 PC 18:1_20:4 PC 18:1_22:6 PC 18:2_18:2 PC 18:2_20:4 PC 31:0 PC 33:0 PC 33:1 PC 34:4 PC 36:4 PC 37:2 PC 37:4 PC 38:5 PC 38:6 PC 40:5 PE 16:0_18:1 PE 16:0_20:4 PE 16:0_22:6 PE 18:0_18:1 PE 18:0_18:2 PE 18:0_20:4 PE 18:0_22:4 PE 18:0_22:5 PE 18:0_22:6 PE 18:1_18:1 PE 18:1_22:6 PS 18:0_20:4 PS 18:0_22:6 PS 36:1 PS 36:2 SM d16:1_16:0 SM d18:1_18:0 SM d32:1 SM d33:1 SM d34:0 SM d34:1 SM d34:2 SM d35:1 SM d36:0 SM d36:2 SM d37:1 SM d38:0 SM d38:1 SM d38:2 SM d39:1 SM d40:1 SM d40:2 SM d41:1 SM d41:2 SM d41:3 SM d42:1 SM d42:2 SM d42:3 TG 14:0_16:0_18:1 TG 15:0_16:0_18:1 TG 16:0_16:0_17:0 TG 16:0_16:0_18:1 TG 16:0_16:1_18:1 TG 16:0_16:1_18:2 TG 16:0_17:0_18:0 TG 16:0_17:0_18:1 TG 16:0_17:1_18:1 TG 16:0_18:0_18:1 TG 16:0_18:0_20:0 TG 16:0_18:1_18:1 TG 16:0_18:1_18:2 TG 16:0_18:1_20:4 TG 16:0_18:2_18:2 TG 17:0_18:1_18:1 TG 18:0_18:0_18:1 TG 18:0_18:1_18:1 TG 18:0_18:1_20:4 TG 18:2_18:2_18:2 TG 18:2_18:2_18:3 TG 46:1 TG 46:2 TG 47:1 TG 48:1 TG 48:2 TG 49:1 TG 49:2 TG 50:2 TG 54:5 TG 56:3 METABOLITES_END #END