#METABOLOMICS WORKBENCH dandanwang2022_20240108_132351 DATATRACK_ID:4563 STUDY_ID:ST003063 ANALYSIS_ID:AN005018 PROJECT_ID:PR001909 VERSION 1 CREATED_ON February 1, 2024, 11:07 am #PROJECT PR:PROJECT_TITLE Uncoupling Metabolic Health from Thermogenesis via BCAA Nitrogen Flux in Brown PR:PROJECT_TITLE Fat PR:PROJECT_SUMMARY Brown adipose tissue (BAT) is best known for its role in thermogenesis. While PR:PROJECT_SUMMARY many studies in rodents have shown tight associations between the metabolic PR:PROJECT_SUMMARY benefits of BAT and increased whole-body energy expenditure, recent evidence in PR:PROJECT_SUMMARY humans suggests that BAT is protective against Type 2 diabetes independent of PR:PROJECT_SUMMARY body-weight. The mechanism underlying this dissociation remains unclear. Here, PR:PROJECT_SUMMARY we report that impaired mitochondrial catabolism of branched-chain amino acids PR:PROJECT_SUMMARY (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, SLC25A44), PR:PROJECT_SUMMARY sufficiently attenuated insulin sensitivity without affecting whole-body energy PR:PROJECT_SUMMARY expenditure and body-weight. We found that brown adipocytes catabolized BCAA in PR:PROJECT_SUMMARY the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, PR:PROJECT_SUMMARY alanine, N-acetyl amino acids, and one of the products, glutathione. On the PR:PROJECT_SUMMARY other hand, the contribution of BCAA as a carbon source to the TCA cycle was PR:PROJECT_SUMMARY incremental. Impairment of mitochondrial BCAA nitrogen flux in BAT resulted in PR:PROJECT_SUMMARY increased oxidative stress and decreased insulin signaling in the liver, as well PR:PROJECT_SUMMARY as decreased levels of BCAA-nitrogen derived metabolites in circulation. PR:PROJECT_SUMMARY Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of PR:PROJECT_SUMMARY BCAA-derived metabolites in the BAT, while cold-induced BAT activity is coupled PR:PROJECT_SUMMARY with an active synthesis of these metabolites. Together, the present work PR:PROJECT_SUMMARY uncovers a mechanism through which brown fat regulates metabolic health via PR:PROJECT_SUMMARY BCAA-derived nitrogen carriers that act on the liver, independent of PR:PROJECT_SUMMARY thermogenesis. PR:INSTITUTE BIDMC PR:LAST_NAME Wang PR:FIRST_NAME Dandan PR:ADDRESS 3 Blackfan Circle, Boston, MA, 02115, USA PR:EMAIL dandanwang2022@gmail.com PR:PHONE 5083733714 #STUDY ST:STUDY_TITLE Serum metabolomics from control and MBC UCP1-KO ST:STUDY_SUMMARY Targeted metabolomics in serum from high-fat diet fed control and MBCUCP1 KO ST:STUDY_SUMMARY mice. N = 6 for control and 7 for MBCUCP1 KO. Statistic: unpaired t-test. Data ST:STUDY_SUMMARY represented as z-score heatmap with each cell representing quantitated value for ST:STUDY_SUMMARY each mouse. ST:INSTITUTE BIDMC ST:LAST_NAME Wang ST:FIRST_NAME Dandan ST:ADDRESS 3 Blackfan Circle, Boston, MA, 02115, USA ST:EMAIL dandanwang2022@gmail.com ST:PHONE 5083733714 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #FACTORS #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 - serum-Con-1 Genotype:Control RAW_FILE_NAME=serum-Con-1.d SUBJECT_SAMPLE_FACTORS - serum-Con-2 Genotype:Control RAW_FILE_NAME=serum-Con-2.d SUBJECT_SAMPLE_FACTORS - serum-Con-3 Genotype:Control RAW_FILE_NAME=serum-Con-3.d SUBJECT_SAMPLE_FACTORS - serum-Con-4 Genotype:Control RAW_FILE_NAME=serum-Con-4.d SUBJECT_SAMPLE_FACTORS - serum-Con-5 Genotype:Control RAW_FILE_NAME=serum-Con-5.d SUBJECT_SAMPLE_FACTORS - serum-Con-6 Genotype:Control RAW_FILE_NAME=serum-Con-6.d SUBJECT_SAMPLE_FACTORS - serum-KO-1 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-1.d SUBJECT_SAMPLE_FACTORS - serum-KO-2 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-2.d SUBJECT_SAMPLE_FACTORS - serum-KO-3 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-3.d SUBJECT_SAMPLE_FACTORS - serum-KO-4 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-4.d SUBJECT_SAMPLE_FACTORS - serum-KO-5 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-5.d SUBJECT_SAMPLE_FACTORS - serum-KO-6 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-6.d SUBJECT_SAMPLE_FACTORS - serum-KO-7 Genotype:MBC UCP1-KO RAW_FILE_NAME=serum-KO-7.d #COLLECTION CO:COLLECTION_SUMMARY Approximately 20 μL of blood was collected from the tail into tubes containing CO:COLLECTION_SUMMARY clotting activator (Starstedt Inc, 16.440.100). The blood samples were kept on CO:COLLECTION_SUMMARY ice and the serum was separated by centrifugation at 3,000 g for 10 min at 4 CO:COLLECTION_SUMMARY ˚C. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY No treatment. All animal experiments conducted were performed in compliance of TR:TREATMENT_SUMMARY protocols approved by the Institutional Animal Care and Use Committee at Beth TR:TREATMENT_SUMMARY Israel Deaconess Medical Center (028-2022). All mice were housed under a 12 h TR:TREATMENT_SUMMARY – 12 h light/dark cycle. Room-temperature mice were housed at 23˚C in TR:TREATMENT_SUMMARY ventilated cages with an ACH of 25. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Serum metabolites were extracted using a 1:4 ratio of plasma to methanol SP:SAMPLEPREP_SUMMARY extraction buffer. After centrifugation at 16,000 g for 15 minutes at 4°C, the SP:SAMPLEPREP_SUMMARY supernatant was collected for LC-MS analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Agilent 1260 Infinity HPLC CH:COLUMN_NAME Waters Atlantis Silica HILIC (150 x 2.1mm, 3um) CH:SOLVENT_A 100% water; 10 mM ammonium formate and 0.1% formic acid CH:SOLVENT_B 100% acetonitrile; 0.1% formic acid CH:FLOW_GRADIENT 5% mobile phase A (10 mM ammonium formate and 0.1% formic acid in water) for 0.5 CH:FLOW_GRADIENT minute followed by a linear gradient to 40% mobile phase B (acetonitrile with CH:FLOW_GRADIENT 0.1% formic acid) over 10 minutes. CH:FLOW_RATE 250 µL/min CH:COLUMN_TEMPERATURE 25 °C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 4000 QTrap MS:INSTRUMENT_TYPE QTRAP MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS MS analyses are carried out using electrospray ionization in the positive ion MS:MS_COMMENTS mode using scheduled MRM method. Multiquant software (version 3.0.3, Sciex) was MS:MS_COMMENTS used for automatic peak integration followed by manual review of all peaks for MS:MS_COMMENTS quality of integration. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples serum-Con-1 serum-Con-2 serum-Con-3 serum-Con-4 serum-Con-5 serum-Con-6 serum-KO-1 serum-KO-2 serum-KO-3 serum-KO-4 serum-KO-5 serum-KO-6 serum-KO-7 Factors Genotype:Control Genotype:Control Genotype:Control Genotype:Control Genotype:Control Genotype:Control Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO Genotype:MBC UCP1-KO 1,5-AG / 1-deoxyglucose 20676.01874 30173.16812 25279.23383 27893.29962 31223.37037 24662.64256 30109.8992 31619.83129 27024.42063 23054.20849 30255.68644 20483.97556 27646.68802 11(12)-EET 3289.286101 1997.221519 1118.026462 8601.717221 2341.796445 2021.866966 5207.207957 1326.999327 2565.394171 1283.52144 544.0073719 863.67014 958.6552856 12-Oxo-ETE 1250.695931 1417.161098 1685.213272 2736.055856 1657.344566 1021.051833 3919.975572 815.1423547 1083.740227 668.8145627 732.1245009 573.0260361 662.1026311 14(15)-EET 975.3384551 565.7324378 403.4570025 1873.845226 451.8096297 353.8204057 1098.289157 380.5679104 477.2311184 338.9377549 66.92004251 280.9943229 258.1727163 15-Oxo-ETE 0 0 0 0 0 0 0 0 20-Hydroxy-N-Arachidonoyl Taurine 1622.592019 1218.19089 1181.185908 969.8522229 1360.014207 1327.116125 1731.63129 2007.041333 1387.153347 1095.693821 1204.412192 1019.927881 872.1683416 2-Aminoadipic acid 7916.388295 28552.04047 16589.81368 17168.35264 17448.51475 15455.98643 19813.1722 20208.69583 16596.59065 23335.15141 22425.28299 7043.388842 18489.2085 2-Deoxyuridine 13338.10906 22251.77216 23159.39288 26155.40906 30004.66061 36669.53509 25526.70013 26407.83856 21814.91202 26967.12659 30762.06111 20759.74907 30164.25497 2-Hydroxybutyric acid 6219.057419 13413.53904 10735.67039 7808.881098 7763.009144 9231.619093 13272.52934 12016.11534 11491.40168 12775.02002 13932.8837 10274.74727 11270.082 2-Hydroxyglutaric acid 340793.3794 380598.6583 289342.3876 270413.1857 276688.4723 258649.3331 334956.2522 371319.0961 286558.392 239022.0558 283899.7777 236721.4183 215586.9725 2-ketoisovaleric acid KIV 9192.849861 6520.930785 6919.78518 5392.203233 7696.889149 7834.658022 6690.132853 7652.917537 7566.259754 7886.362099 7720.153621 5797.976336 5817.182901 3-Aminoisobutyric acid 0 0 0 0 0 0 0 0 0 0 0 0 3-Hydroxybutyric acid 190134.3674 183106.4238 263170.1412 92495.20497 114600.7847 82236.9591 330009.0048 490596.3946 335351.5053 264321.0742 216964.816 83992.46537 207265.8841 5(6)-EET 602.7955783 420.7545436 429.0733593 844.7154061 495.5982704 221.6613463 747.7336918 467.357908 396.6297565 707.2876149 484.4805183 473.3836509 373.3379104 5-MTHF 2022.785749 3478.403351 3913.074624 2891.188241 3174.112421 3115.247946 1048.643989 2088.48403 2485.512912 4312.411555 4093.52906 3973.404019 3142.990904 5-Oxo-ETE 1267.116285 760.9816125 982.4857891 1200.467847 1356.131505 792.2722136 1665.381525 814.6822926 1010.807574 755.9267991 846.6416757 952.2807965 846.6699022 8(9)-EET 1455.636366 1479.166909 955.5842681 4090.282956 1423.454335 1387.263729 3041.652093 859.559779 1373.0913 618.5003082 494.7951829 349.4196618 690.7348279 Acetoacetic acid 2458.556815 2203.74705 3983.799307 1283.010741 1528.981003 1214.472032 3349.922217 6748.283313 4141.276531 1688.822854 3201.367284 1596.087584 3053.613102 Aconitic acid 1109521.2 734655.1445 779740.7685 764333.3543 589622.3658 596270.8863 781478.8524 682127.7956 763123.8693 592012.9565 493431.2435 690262.6604 564731.4974 Adenine 136.2509901 372.0610919 208.5998115 193.5065722 327.7831319 396.9743868 295.4863232 381.5826492 351.7401839 341.2616832 267.1986275 208.6169674 369.9315396 Adipic acid 2841.839824 4141.179457 4346.596172 4525.632118 5457.991885 5805.848237 3285.44702 3830.191303 3888.336486 3889.240425 3913.334837 3581.660476 4666.218272 ADP 3099.420994 1892.266894 1262.802717 3101.223446 2102.637692 1889.535777 2579.904826 1603.635246 1708.639892 1659.403258 861.4422455 1093.22525 979.8201032 a-Ketoglutaric acid 1656839.105 1487520.941 1329193.605 878516.936 1066257.167 1285964.392 1099337.231 1497425.509 1168961.843 1291269.691 1409278.597 1720666.86 973857.1781 Allantoin 281079.7625 284455.5521 296997.968 260457.7842 326748.9775 330909.804 239313.5547 271361.9647 264666.329 327767.2543 244789.1165 297177.9882 267943.0627 AMP 775319.9221 51919.18669 477254.413 2059575.969 475433.1291 215255.3578 228291.8154 84389.79343 437575.403 216707.6047 3356.932704 90031.64296 242894.3972 Anthranilic acid 5040.213893 4135.241182 4032.385464 4641.393997 5578.727333 3805.615482 3671.061873 3542.024886 3194.253848 2440.20657 4057.047317 2397.160812 2777.627021 Arachidonic acid 403770.2818 439116.8969 423181.8433 353920.4193 365265.8837 320855.1819 428238.3757 376040.7099 465073.2981 415121.8228 413320.4523 338282.9731 323802.9908 Arachindonoyl Phenylalanine 205.3475841 109.6989025 87.26094897 128.4453099 128.3457294 112.8049741 129.5522434 59.20581701 134.746647 114.7561167 59.5697158 112.0085261 166.3135058 Aspartic acid 59141.17112 61152.67224 62953.9178 84230.39999 71462.64434 52485.91634 46908.68638 40662.50387 41487.60164 43374.62622 53918.04106 47076.07851 55223.74649 Atorvastatin 0 0 0 0 0 0 0 0 0 0 0 0 0 ATP 416.4390501 334.3813988 223.4902583 370.2741517 240.4687971 752.1852817 429.4672678 319.5156236 219.1512716 246.0250299 256.7278769 240.0711815 BHB-Leu 0 0 243.9225814 1335.253856 386.0714216 253.9135566 132.015892 170.6028337 298.2111991 207.6860533 214.6827212 462.6570007 BHB-Met 0 0 0 0 0 0 0 BHB-Phe 1428.8594 3660.447787 3265.776927 1070.532022 2788.076758 2297.984288 4011.174655 3608.646735 4488.254383 4960.402285 3540.222663 3036.29636 3194.620868 BHB-Val 2375.618095 2133.623934 1175.959751 2613.935586 2213.187454 2580.006791 2092.243246 1499.050911 1623.930567 1487.287881 1287.954665 1231.196404 2449.671974 Bilirubin 36239.51249 27440.65933 23530.87813 13679.9592 10395.70421 14752.11662 24517.03021 23372.96626 23088.24346 24453.82877 20114.40945 23435.65428 43242.51958 Butyric acid 30339.43467 42742.34697 42811.15758 32741.86902 44683.08888 36892.06178 33195.57079 35553.23936 40773.72719 39946.43152 43704.11988 33273.82892 36417.30719 C12-Phe 0 0 0 0 0 0 0 C15-Phe 0 0 0 0 0 0 0 C16-Phe 1342.184825 934.4941503 881.2334302 777.4417004 949.8851836 921.6378488 1164.756918 1287.281172 948.2550505 740.3461292 724.2782826 1159.763827 1198.124403 C18:1-Asn 1519.727021 1347.115792 1541.717876 1261.930121 1368.765914 781.3990721 1658.717954 1058.35436 930.4327997 1214.952054 652.1253054 982.3573358 1524.021561 C18:1-Gln 6389.389698 9463.04621 10916.96235 6432.149881 8379.04539 5214.154428 6551.96236 7374.794423 8378.669501 5325.07081 10827.32455 6620.120474 3735.544433 C18:1-Glu 867.2349401 1350.153877 1117.081342 1195.061583 1012.644923 1325.041874 1199.730448 1452.32234 1126.34381 799.6142217 1447.19368 814.7266249 910.7722758 C18:1-Ile 975.611385 1265.793939 618.559584 845.9978939 843.124303 789.4967559 769.8780688 581.6481611 767.725225 817.0644513 727.6757358 703.5003035 586.8859399 C18:1-Lys 0 0 0 0 0 0 0 0 C18:1-Met 859.6759542 746.9808635 575.4829916 756.6432085 593.3893801 512.4531943 1064.728106 621.5742504 752.0940037 585.9468643 741.3657353 568.580635 686.0495184 C18:1-Pro 30231.92135 14775.85898 15748.31393 22307.68806 22193.43819 14888.11279 32022.91149 25538.55456 18744.7674 26291.08873 14437.65338 15258.14975 17876.99978 C18:1-Ser 1188.819847 914.8915437 1092.449409 496.0992478 771.8861104 687.7224667 810.1187094 672.3860334 548.7769168 920.0662359 1079.570176 739.2879459 752.7942382 C18:1-Trp 0 0 0 0 0 0 0 0 0 0 0 0 C18:1-Tyr 724.9779782 361.9164798 337.1614793 510.9347108 373.608965 427.8386135 695.9513211 499.5333188 271.7979082 302.173783 475.8593031 354.8796253 356.2363962 C18:2-Phe 931.9245611 460.2791899 857.7200685 729.2692259 680.5050848 674.357857 910.9718523 814.9333283 736.2925812 380.2824955 809.1366258 726.3631803 785.7638724 C18:3-Phe 8594.639109 7811.297258 7722.604747 11156.47342 6576.959396 5567.683196 10435.89191 6622.306387 7575.729229 7701.329996 7004.897198 7673.453258 6836.631719 C20:4-Gly 0 0 0 0 0 0 0 0 C20:4-Phe 162.3544907 130.4452629 75.17243586 12.78075209 175.9921805 107.8037631 108.2791331 146.2304328 161.6342071 145.3178314 147.3011412 129.9328287 172.0997958 C20:4-Ser 0 0 0 0 C20-Phe 0 0 0 0 0 0 0 0 0 0 0 0 C22-Phe 523.0641108 482.946408 571.9582792 566.2364578 618.5247697 364.6839418 891.9580943 398.1719854 468.2346049 454.5307079 331.9432698 467.0703075 432.9651242 CDP-Choline 560.2106765 343.493299 711.9756324 1178.773959 339.9614775 214.0136112 2135.579316 149.7239428 219.5172104 398.2929692 25.38388526 280.8372303 166.0906222 Cholic acid 361591.1976 15181.37315 4135.196024 1472.601518 10734.38616 1613.691779 20137.31483 1757.842738 1694.718501 797.9145643 2695.226252 285298.6302 8275.033288 Citraconic acid 8285.584116 10495.35204 11261.64136 9953.618693 16591.39608 10406.89524 10606.41227 10296.69957 12640.02108 10668.2559 9693.05881 8370.251922 8678.475149 Citric acid/Isocitric acid 26884307.73 29361572.56 27981771.48 28111947.67 27242043.18 23456237.93 20660959.07 21789238.41 25648323.7 23507739.47 23496280.25 27866594.95 25938915.43 Citrulline 465636.5313 663758.0031 497824.5976 349677.9009 546867.3756 659865.268 515794.1564 608282.0242 499318.5139 574559.1321 702906.9653 679649.5245 470645.745 Citrulline-d7 86961.01072 104870.7832 107117.6952 83986.92698 86645.89171 109148.306 122873.9203 129687.3153 126273.5659 118943.3795 124963.3021 85188.82156 90862.36619 cyclic-AMP 844.4157498 842.9847232 630.2671216 1119.7347 915.1050856 1783.676928 779.0990291 823.2386625 621.2188969 2864.826072 968.8101947 2647.060284 4043.868582 DDHAP/Glyceraldehyde-3-P 49124.69368 43949.402 41295.2562 103690.1742 39236.81989 24904.29088 67624.69826 24963.248 29057.80395 13302.26977 17586.9466 16011.3557 19370.66632 Deoxycholic acid 66936.23352 22012.18808 10984.04049 2645.689949 5743.575032 4866.274158 1872.145895 3907.742541 978.2753931 3833.602461 4585.981801 65034.79835 2759.449729 D-Gluconic acid 1562949.327 2618019.865 2650457.118 3028779.639 3065316.076 2558281.436 2468290.313 2792527.927 3033537.927 2517590.347 2490301.995 1677810.965 2473957.354 DHA 1360750.485 1446391.439 1512442.998 883465.2692 1442141.67 956765.1026 1245953.851 1252981.838 1539006.053 1402717.516 1356469.469 1006012.867 1020353.543 DiHOME 4927.01245 1162.221838 1680.4221 1124.365514 2333.862716 1332.074723 1458.849393 1524.023735 3092.279918 2373.168623 1636.811441 968.9588128 1129.059662 Dihomo-Gammi-Linolenoyl Ethanolamide 2823.908369 2182.781926 2242.026418 2276.165629 2632.874907 2277.72588 2768.72471 3339.966673 3068.406122 2500.263867 3516.771485 1630.914667 2351.208504 EPA 7433.626882 9389.056715 10534.50444 6977.688677 9499.024462 8086.861705 9375.111376 7679.449307 11911.81356 10235.30762 9310.923005 5160.236443 9570.419821 Fumaric acid 19122.0955 12758.38837 8025.607648 14193.95276 9417.278855 11458.01353 14863.1368 9946.199851 11429.47554 11227.13179 7846.478145 12591.06608 10287.2717 Glucose/Fructose/Galactose_waterloss 79895.26678 114030.687 133124.1228 87472.06407 126015.1571 114709.1819 90591.16159 98047.22793 111667.5887 136695.5901 130009.9456 103665.2955 97493.57601 Glutamic acid 244427.274 340580.0652 314825.977 375546.8318 309472.0874 288977.5729 251283.7222 196213.5697 189607.7191 189305.2386 283794.6194 243734.1173 285349.4847 Glutathione Disulfide 19180.93898 18351.0875 15520.33542 33866.17191 15248.97712 9562.578987 18939.21071 8518.736667 11036.07536 10056.84273 9393.927747 6755.491812 11291.20837 Glutathione_reduced 58704.87362 35644.9426 37942.86935 50158.10989 55487.00854 43840.55723 24954.61466 26881.83652 34418.25215 28727.04084 33293.15449 21320.99333 34493.37959 Glyceric acid 3461.182047 3371.269483 3752.716291 3585.730393 4106.657954 3392.940814 3320.18233 3071.459956 3351.256673 3186.891167 3201.806187 2766.988217 2777.314866 Glycerol-3-phosphate 262056.1947 385907.0448 379931.1876 418231.4548 355299.2861 348858.9618 305028.9175 225994.0258 282356.6133 221919.3409 285474.2789 242143.4143 386346.9008 Glycochenodeoxycholic acid 90894.34804 7032.925244 3166.460211 2915.896259 10062.37208 6264.887243 105295.0349 55712.19928 2427.241165 2511.043597 2709.951423 18354.35915 3741.907275 Glycocholic acid 787831.0012 28636.8344 13945.92912 23193.62544 61660.17683 63940.94085 135975.0299 24299.86926 4473.646291 4860.161022 17070.18269 439450.3014 47210.16968 Glyoxylic Acid 0 0 0 0 0 0 0 0 0 0 0 0 0 HETE 1179644.538 769333.4931 727562.0667 3032731.099 1043094.921 892978.8462 2665503.834 554600.5803 919502.3034 322712.6787 295239.4907 242737.4213 456651.8829 Hippuric acid 2127.140663 3153.260024 5149.901315 3657.463871 16459.3491 24454.24594 5591.360173 4841.036451 3589.475437 3344.868816 7591.870345 9386.219801 12986.57032 Homogentisic acid 1075.478868 1664.108493 1503.89111 1165.614935 2240.405069 1644.528359 908.2726936 1765.191778 2077.059964 1468.801497 1026.935948 643.8330139 727.193671 Hydroxyphenylpyruvic acid 18958.18052 24386.19265 20394.99186 13498.37219 23571.18812 20674.78164 17472.52718 22446.82511 19179.35434 17656.48185 22283.50205 19972.40453 16189.56682 Hypoxanthine 225671.2051 52865.75683 175977.9237 48879.67697 140057.106 22995.27706 148849.0588 9674.251466 17944.1794 23695.81871 571.6829017 9219.084278 21543.01473 IMP 595.5869249 610.8253031 579.5572058 394.1210526 996.0669509 525.4613595 530.6807284 382.317106 437.7841879 505.6546529 527.8816658 214.3158722 316.9567554 Indole-3-carboxylic acid 611.4686889 925.0612498 919.9208332 1351.534468 846.8012955 1070.404288 1039.411636 380.8949148 791.9390752 701.0358012 1195.242304 1042.481596 1144.782012 Indole-3-lactic acid 96390.13587 191286.3742 143496.463 196139.4116 235325.4043 207702.8306 184280.1049 300317.573 231906.8219 181711.5898 131985.8524 87507.16446 203310.1399 Indole-3-propanoic acid 1610.67818 3071.803502 2016.205924 1215.265095 5764.238021 1542.392 406.9653516 169.2734774 1840.43456 2746.102241 2634.81299 3462.923919 3148.364431 Indoxyl-sulfate 448632.3961 847994.8679 824954.5313 284143.086 778863.557 546348.7576 640253.4619 658905.3592 636390.6349 1296854.169 858412.5172 423532.519 645122.1383 Inosine 499482.3056 225407.2669 611218.0412 237909.4871 636158.1036 487062.4839 589772.5962 98810.53702 132369.1924 289141.713 32038.59541 190686.6579 302943.0051 Inosine-15N4 3872409.188 3614563.8 3537002.487 3570953.041 3631974.273 3687360.137 3592797.532 4151262.588 4118867.529 3944810.65 3684155.151 4323356.304 3813582.458 Keto-isocaproic acid KIC / Keto-methylvalerate KMV 16077.99168 41978.57133 35362.38378 39762.90077 46181.55684 47506.94501 43369.95731 34569.24301 35437.9037 42634.2479 39629.31499 25775.40816 39812.86185 Kynurenic acid 97814.59658 90281.31582 59007.74591 88418.12455 81995.2052 78936.27793 112200.1883 162910.0658 119031.2966 82026.73085 74913.57054 51820.03425 73124.14688 Kynurenine 10822.91923 9040.72205 9888.175356 14723.78628 10226.60411 12890.6041 14223.24144 15483.50502 11676.58624 10045.88746 10886.68516 14605.38641 13045.12575 Lac-Arg 282.2807529 281.9769288 317.734554 492.6747213 293.1386976 398.2220562 233.4307865 529.6919884 141.2103955 498.7061667 350.7646028 300.0843382 272.8311571 Lac-Asn 10082.59914 8099.343271 9102.067263 7053.712506 8043.011779 8357.496111 8094.643033 9394.856141 8508.266819 7594.971292 8533.718006 10391.62753 9526.654143 Lac-Asp 5292.094339 5690.349483 5125.338886 6476.28278 4894.519203 2163.858989 4469.750908 3646.503408 4679.796045 3560.081137 3094.021549 1648.710185 2358.346711 Lac-Cys 0 0 0 0 Lac-Gln 14361.82828 20074.34145 18015.22443 21578.55057 14740.01562 14795.19551 17397.40399 21214.42668 20707.43786 16381.20531 18310.01636 16893.04053 17703.47352 Lac-Glu 5532.657931 7423.988217 6512.915599 6196.170873 6312.53309 4808.044616 5263.892948 5503.98662 5796.11949 4554.882709 5185.773663 3293.295486 4458.820458 Lac-His 941.4797006 1140.409921 1113.586918 934.2945603 1258.765546 986.6508375 758.4892122 1114.480011 1106.15726 818.7066127 1077.45474 1078.53248 1316.081557 Lac-Ile/leu 1216.334618 662.4548134 415.0213439 363.1473872 622.6422203 643.3560057 524.8884367 873.3171141 502.9324739 727.7063679 378.8692064 444.4123054 590.0107194 Lac-Lys 363.2160518 318.8595254 310.3430966 251.4735979 281.0796971 229.183124 223.0949036 212.0490464 263.6851639 232.2460613 319.2954685 247.5565266 285.1845766 Lac-Met 2204.252003 2284.070174 1382.074939 3946.137707 2789.071975 2700.348545 2294.075456 2324.849836 2064.448052 2581.584123 1588.487094 2200.772364 2426.809422 Lac-Phe 30694.95639 18752.21762 8875.388644 33558.36997 15778.74667 30154.7119 17577.80006 13862.85307 13703.78405 17834.77722 11026.82742 19364.31925 17595.55191 Lac-Pro 8990.762118 10856.78516 11925.98353 12683.47273 10582.32617 10746.87528 13334.85014 10676.22378 8750.079861 9507.616791 9902.122995 10195.77512 10721.44223 Lac-Ser 1581.454869 1771.479703 1748.296523 1754.277395 2217.852044 1468.026343 1582.707345 1556.715643 1566.557497 1539.886107 1740.434196 1726.880725 1217.099064 Lac-Thr 809.2764812 1409.935637 962.7748374 1116.313182 1313.212701 917.4126704 1096.581315 1098.359232 772.0261556 1675.219589 1291.726864 1180.063054 1329.598538 Lactic acid 4643208.028 4960312.262 4745157.503 5496652.82 4834797.526 4863138.282 4697812.785 4866678.399 3737085.501 4096511.458 4837982.391 4486600.304 4752979.928 Lac-Tyr 90031.44022 60316.57075 33380.68435 73470.56249 53636.11617 84724.99191 54804.67236 43322.46411 44843.40451 39868.56016 36414.27055 75875.45236 46563.78716 Lac-Val 1413.854284 1819.459219 1659.025814 1668.458896 2526.285707 2428.76057 620.5301757 1170.155803 1467.98436 2427.08163 2025.63772 1396.798438 1627.273301 Linoleic acid 93553.60244 89902.37895 93426.8672 88164.97339 94810.07683 88067.22272 83220.08039 94784.36934 103489.6901 92210.09686 84339.6877 69518.76701 93713.16291 Lisinopril 0 0 0 0 0 0 0 0 0 0 0 0 Malic acid 5876883.345 7340717.012 5903853.949 6175123.644 5828829.833 5558142.925 5366849.961 4948258.511 5931873.189 6126130.964 5337098.423 5539316.425 4903878.194 Malonic acid 64285.79726 14105.04032 10854.7281 13240.33486 12846.23671 11338.69568 11864.49865 15031.41613 27534.19734 13127.70339 10260.64716 7887.09023 15269.74712 Mevalonic acid 41466.66283 72917.67503 58835.56271 63530.48336 89119.65836 54943.24934 59505.78901 42690.60971 60330.93146 42943.97773 37779.85366 38609.45469 46037.2458 N-Acetyl-Histidine 172038.0881 94336.69809 98751.64417 105143.919 115554.7898 83186.32216 122409.4262 159904.7146 148711.9196 90023.37502 93018.02406 105857.5729 82291.30613 N-Acetyl-Isoleucine 54411.23961 47062.8701 38204.26712 35061.76414 54863.59449 58247.57465 41832.79431 61191.96119 59601.53475 51745.00785 53898.70553 35895.52176 47485.22452 N-Acetyl-L-Alanine 36211.8202 34904.01604 35723.74121 35937.5685 41865.05348 35220.99494 37299.43507 38082.446 42485.03548 38800.54041 38212.70533 34111.6301 32770.49106 N-Acetyl-L-Aspartic acid 263209.702 250598.6475 213931.9292 255510.6501 194910.2946 157569.7536 262486.1999 204393.5418 193074.7136 225622.7079 163308.475 116344.062 139125.9917 N-Acetyl-L-Glutamic acid 62976.28044 130874.4056 84304.42162 92407.49767 90182.81544 63424.89416 106025.0231 166855.7681 111731.6935 91961.3809 80324.25436 33619.58316 44385.99051 N-Acetyl-L-Glutamine 58750.83993 57463.11062 55051.60532 83775.8345 62697.91339 54707.53639 55655.88133 52585.43455 56564.83808 49666.99823 57213.86468 52707.07478 54962.19917 N-Acetyl-L-Glycine 176070.4095 125413.9038 98826.03701 134611.1339 93773.9131 97839.51951 121279.1174 169889.5569 192801.7967 143298.3551 97302.01693 80044.36386 140590.0033 N-Acetyl-L-Methionine 28969.39858 17538.22804 16655.27486 21670.12566 17010.93591 15572.68085 15860.46687 16560.92701 22208.28916 20868.10555 16982.94212 15972.25307 19012.59296 N-Acetyl-Valine 266.1318141 101.9577836 225.4629252 196.6421359 209.8253192 136.0184377 206.7787645 385.1867425 218.3629148 175.5191127 265.8177395 99.13118567 131.3326009 N-Actyl-D-Glycosamine 73.85076534 63.28689876 223.9517807 96.5414027 232.4383057 343.5597235 326.3984489 230.9913818 217.8436382 190.684287 231.6021246 299.0400136 177.1722828 N-Arachidonoyl Dopamine 61.58994443 292.7605856 748.4693279 271.6755923 681.9601707 597.3553339 422.721925 235.2665097 114.606967 506.7280427 1022.68208 1499.879271 576.2325554 N-Arachidonoyl Taurine 5074.358117 8662.155908 6110.849526 4314.377871 7797.003952 6541.129498 4714.646007 5511.740952 5092.832524 5957.486828 5863.920982 4538.488162 4837.603311 N-Docosanoyl Taurine 846.3173393 1505.789391 762.8335802 645.7018615 1087.726088 903.6803914 897.4191632 954.0505695 751.1668456 990.5480266 940.2989663 812.4893665 834.6183639 N-Lignoceroyl Taurine 402.8581928 130.4353705 414.0370438 210.9545482 285.4012057 343.6985739 388.7772083 326.9857674 290.354917 339.8402117 135.6970847 365.7852813 258.0490526 N-Nervonoyl Taurine 364.6759029 149.4585607 231.1191994 137.1142191 268.5732568 315.5720271 332.4411996 219.802054 219.8357539 169.8769334 200.0211237 359.0244487 172.2253332 N-Oleoyl Dopamine 20.88897509 28.96056425 62.85698532 69.29225859 130.2091577 74.62946574 68.60282064 65.42068366 15.9882533 15.94297547 67.77358215 253.8341402 141.0953453 N-Oleoyl Taurine 10920.06692 6599.393453 7409.526656 7788.617417 6502.5018 6125.050498 9267.862692 7856.83633 8256.533012 6170.400011 7873.016359 6021.085717 7882.434262 N-Palmitoyl Taurine 6510.9404 6418.881125 7005.64007 5356.355698 7083.892613 5458.233061 7475.184488 6167.883159 6764.855667 9305.864177 6334.69581 4487.781268 6614.705449 Oleamide 574.7867494 357.7806902 458.6559398 356.4476236 302.7266651 267.5068747 347.8953766 119.1217321 409.9167718 320.6730281 516.0961183 190.4458348 293.4642772 Oleoyl Glycine 3622.906779 1598.172389 2070.453424 1317.943455 1811.205341 1604.773702 1646.386401 1924.61132 2197.273543 1681.744955 2056.728726 1973.770515 1899.433028 Oleoyl Leucine 2013.811556 1668.090682 1714.864081 1610.552475 1730.405492 1572.547074 2294.21064 2101.55789 2449.3183 1651.798408 2154.439347 1399.488504 2404.434486 Oleoyl Phenylalanine 1246.571793 803.4217532 1179.15369 931.4337697 824.2047839 907.6425939 1357.153229 993.7428606 922.130953 956.4917642 858.3379576 1136.449142 1408.931547 Oleoyl Serine 1789.022016 1046.916643 1384.788009 724.3107015 1095.952129 1102.914257 791.536574 1086.935512 1072.668619 1508.700011 1512.577974 1361.638218 1023.774209 Orotic acid 367069.6693 393748.0568 406387.5036 322917.6047 431451.87 309808.8194 283166.5824 357159.0454 427361.4027 438571.7062 331493.736 299006.2552 349787.5678 Oxalic acid 3323.620801 4291.820621 4508.83409 8699.825173 5307.64978 2550.966037 2364.560801 3715.828035 4073.788435 3446.297008 3677.355001 4393.03595 2967.849108 Oxaloacetic acid 26130.05482 22611.92749 27796.01994 23643.24165 22071.6204 20756.02162 26606.30202 31638.40609 27818.61161 18953.80204 30723.22788 31544.19083 22776.43193 Oxypurinol 0 0 0 0 0 0 Palmitic acid 18843692.78 21147224.26 20542494.48 14242938.27 22149405.75 18730920.16 21291325.78 22166051.05 22861170.14 19855609.37 20013490.79 17111613.04 19038357.17 Pantothenic acid 250760.4539 424808.8441 381273.2914 768858.2118 417817.0898 432281.6932 261537.8922 266184.9926 316109.3325 367054.4963 430502.8802 386246.941 517305.4887 Phe-d8 121651.7564 127763.7112 130369.9726 122603.3352 129257.2706 127069.7928 140478.0777 129595.4328 129259.4998 131059.2489 122617.249 125019.2347 128139.8783 Phosphocreatine 28487.93119 37429.77277 32130.35937 20830.61504 34071.50851 38568.47983 16882.62057 24674.54337 26775.23991 36756.41082 32456.58017 40526.65102 41827.90523 Pravastatin 0 0 0 0 0 0 0 0 0 0 0 Pseudouridine 1817192.392 1283936.345 1870240.17 1378238.776 1399500.476 1085682.074 1357010.595 1504748.733 1683086.06 1846265.101 1219423.577 1365459.097 1109580.523 Pyroglutamic acid 2666.45444 2869.156262 2293.39403 4202.751742 2565.931829 2332.540089 4408.101837 2181.620891 3047.514704 2521.772174 3012.989443 1890.672035 2118.636627 Pyruvic acid 42726.12812 46397.8627 52067.75888 49313.91217 50637.1833 48549.92431 39331.13057 48649.17373 24467.33545 30228.93168 48177.42381 44364.4997 45190.55642 Quinolinic acid 20256.4142 35751.20939 31550.54326 35205.87599 33815.6505 27373.87927 47733.96621 85234.29962 33782.60662 30376.09114 35253.74715 18470.83394 20706.00419 Saccharopine 9793.79629 18264.85807 23240.97337 22906.48259 37910.91195 41961.34495 13002.10137 14861.77296 16268.62181 17595.06955 26365.53021 19842.6571 36688.5123 S-Adenosyl-L-homocysteine 1714.740498 1628.789076 1574.113486 1932.046017 1739.730597 1668.867266 1975.615502 2336.333496 2028.307913 1667.362084 1400.949606 1144.876522 1360.933608 Salicylic acid 0 0 0 0 0 0 Simvastatin 0 0 0 0 0 0 0 0 0 0 0 0 0 Stearic acid 12974619.29 10202572.85 10145865.72 7268803.022 10401759.13 7565180.078 10997000.79 10609529.5 10205743.65 9725589.859 9154472.874 9837213.154 8608229.088 Succinic acid/Methylmalonic acid 113090.5079 108702.0235 65291.37995 172203.0608 91174.55339 123639.7632 120801.7663 69485.37337 83504.55377 64209.14701 70926.91692 62098.95448 156404.9694 T3 680.6360651 2346.552746 2352.311356 2537.685628 1483.167215 1036.656851 1789.535249 1474.141876 2517.807032 2154.109806 2268.183502 682.9452745 2208.188365 T4 4052.355181 10963.7917 13708.2264 11861.0693 9918.82968 8910.305318 7289.593864 9382.629986 12132.57097 13196.22123 10574.05519 3611.413851 10637.20012 Taurine 7321343.872 7720202.893 8404513.429 7262645.319 7687659.398 8451759.901 7836353.431 6819119.331 6114690.591 6693949.539 7636680.797 8000905.574 7647283.976 Taurocholic acid 1484667.576 114913.9582 80356.57436 94579.571 204580.9088 539329.9577 422554.9658 70418.78891 12680.2817 17597.94028 117897.1724 1846706.089 200724.8406 Taurodeoxycholic acid / Taurochenodeoxycholic acid 17132.57223 33392.52158 24366.70477 24346.06475 26668.23522 24652.34217 42839.81063 40439.69247 23451.91338 23736.2978 30363.92149 16692.51327 27016.35436 Thymidine 1592.913545 2006.474063 2067.446708 2151.140492 2124.668295 1263.162594 2217.140917 1919.07147 2665.372532 1811.812576 1099.705224 861.1028083 1860.227199 Thymine-d4 251234.7717 272993.0436 275199.8103 283747.0801 289616.8709 305844.8726 284769.8132 299691.3186 284118.3689 286473.2243 280667.2688 267744.4489 295502.2641 UDP-GlcNAc 5901.901308 5271.351373 5624.908449 19242.13834 9270.99284 4588.584582 12269.54427 3989.09047 4349.523583 3753.257639 338.1033453 2821.72906 6789.163865 UDP-glucose / -galactose 15720.14502 4269.015502 11395.74215 27519.59248 14618.02513 3676.632452 11469.82812 4274.891813 7165.387255 4770.498404 311.5015147 2919.411633 7446.553328 Uracil 45215.98673 47584.11036 40716.147 53304.60258 49869.8839 66096.73245 51323.70318 41720.02101 46897.98177 37232.26837 31945.04436 31514.84842 38575.14036 Uric acid 2192696.741 2279558.624 1741825.632 2490997.552 2212003.92 2824469.394 2666262.136 1961207.631 1870431.601 1823755.508 1584713.771 1960146.269 2084280.09 Uridine 73195.24072 140897.6386 100660.4057 177091.8446 198953.7105 198847.4623 205858.3072 166459.0076 219966.0336 165917.1745 119359.3196 170852.4089 274673.1753 Warfarin 0 0 0 0 0 0 0 0 0 0 Xanthine 738403.1293 223004.6798 417139.144 121997.6841 331765.7641 75882.04612 454844.9738 28937.64796 85343.08518 98799.96352 1877.644774 48347.03441 74278.3178 Xanthosine 18972.61874 16995.00433 12392.42953 29787.43299 20031.45754 31689.51565 33914.98431 9143.499277 14756.10269 9450.935498 8025.565608 6409.419843 22401.96353 Xanthurenic acid 68261.49252 64333.36211 44842.40657 51465.94408 78361.49504 51676.45863 61558.49119 108630.9528 96038.27602 54729.68671 50073.42206 46646.80048 43204.11903 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 1,5-AG / 1-deoxyglucose 11(12)-EET 12-Oxo-ETE 14(15)-EET 15-Oxo-ETE 20-Hydroxy-N-Arachidonoyl Taurine 2-Aminoadipic acid 2-Deoxyuridine 2-Hydroxybutyric acid 2-Hydroxyglutaric acid 2-ketoisovaleric acid KIV 3-Aminoisobutyric acid 3-Hydroxybutyric acid 5(6)-EET 5-MTHF 5-Oxo-ETE 8(9)-EET Acetoacetic acid Aconitic acid Adenine Adipic acid ADP a-Ketoglutaric acid Allantoin AMP Anthranilic acid Arachidonic acid Arachindonoyl Phenylalanine Aspartic acid Atorvastatin ATP BHB-Leu BHB-Met BHB-Phe BHB-Val Bilirubin Butyric acid C12-Phe C15-Phe C16-Phe C18:1-Asn C18:1-Gln C18:1-Glu C18:1-Ile C18:1-Lys C18:1-Met C18:1-Pro C18:1-Ser C18:1-Trp C18:1-Tyr C18:2-Phe C18:3-Phe C20:4-Gly C20:4-Phe C20:4-Ser C20-Phe C22-Phe CDP-Choline Cholic acid Citraconic acid Citric acid/Isocitric acid Citrulline Citrulline-d7 cyclic-AMP DDHAP/Glyceraldehyde-3-P Deoxycholic acid D-Gluconic acid DHA DiHOME Dihomo-Gammi-Linolenoyl Ethanolamide EPA Fumaric acid Glucose/Fructose/Galactose_waterloss Glutamic acid Glutathione Disulfide Glutathione_reduced Glyceric acid Glycerol-3-phosphate Glycochenodeoxycholic acid Glycocholic acid Glyoxylic Acid HETE Hippuric acid Homogentisic acid Hydroxyphenylpyruvic acid Hypoxanthine IMP Indole-3-carboxylic acid Indole-3-lactic acid Indole-3-propanoic acid Indoxyl-sulfate Inosine Inosine-15N4 Keto-isocaproic acid KIC / Keto-methylvalerate KMV Kynurenic acid Kynurenine Lac-Arg Lac-Asn Lac-Asp Lac-Cys Lac-Gln Lac-Glu Lac-His Lac-Ile/leu Lac-Lys Lac-Met Lac-Phe Lac-Pro Lac-Ser Lac-Thr Lactic acid Lac-Tyr Lac-Val Linoleic acid Lisinopril Malic acid Malonic acid Mevalonic acid N-Acetyl-Histidine N-Acetyl-Isoleucine N-Acetyl-L-Alanine N-Acetyl-L-Aspartic acid N-Acetyl-L-Glutamic acid N-Acetyl-L-Glutamine N-Acetyl-L-Glycine N-Acetyl-L-Methionine N-Acetyl-Valine N-Actyl-D-Glycosamine N-Arachidonoyl Dopamine N-Arachidonoyl Taurine N-Docosanoyl Taurine N-Lignoceroyl Taurine N-Nervonoyl Taurine N-Oleoyl Dopamine N-Oleoyl Taurine N-Palmitoyl Taurine Oleamide Oleoyl Glycine Oleoyl Leucine Oleoyl Phenylalanine Oleoyl Serine Orotic acid Oxalic acid Oxaloacetic acid Oxypurinol Palmitic acid Pantothenic acid Phe-d8 Phosphocreatine Pravastatin Pseudouridine Pyroglutamic acid Pyruvic acid Quinolinic acid Saccharopine S-Adenosyl-L-homocysteine Salicylic acid Simvastatin Stearic acid Succinic acid/Methylmalonic acid T3 T4 Taurine Taurocholic acid Taurodeoxycholic acid / Taurochenodeoxycholic acid Thymidine Thymine-d4 UDP-GlcNAc UDP-glucose / -galactose Uracil Uric acid Uridine Warfarin Xanthine Xanthosine Xanthurenic acid METABOLITES_END #END