#METABOLOMICS WORKBENCH johru_20240219_051021 DATATRACK_ID:4663 STUDY_ID:ST003105 ANALYSIS_ID:AN005084 PROJECT_ID:PR001928 VERSION 1 CREATED_ON February 19, 2024, 5:35 am #PROJECT PR:PROJECT_TITLE Activation of GFRAL+ Neurons Induces Hypothermia and Glucoregulatory Responses PR:PROJECT_TITLE Associated with Nausea and Torpor PR:PROJECT_SUMMARY GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity PR:PROJECT_SUMMARY treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If PR:PROJECT_SUMMARY GFRAL+ neurons acutely regulate glucose and energy homeostasis is however PR:PROJECT_SUMMARY underexplored. Here, we report that cell-specific activation of GFRAL+ neurons PR:PROJECT_SUMMARY using a variety of techniques causes a torpor-like state, including hypothermia, PR:PROJECT_SUMMARY the release of stress hormones, a shift from glucose to lipid oxidation, and PR:PROJECT_SUMMARY impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose PR:PROJECT_SUMMARY uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of PR:PROJECT_SUMMARY blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, PR:PROJECT_SUMMARY insulin signaling, adipose tissue differentiation and mitogenesis, and energy PR:PROJECT_SUMMARY fluxes. Our findings reveal that acute GFRAL+ neuron activation induces PR:PROJECT_SUMMARY endocrine and gluco- and thermoregulatory responses associated with nausea and PR:PROJECT_SUMMARY torpor. While chronic activation of GFRAL signaling promotes weight loss in PR:PROJECT_SUMMARY obesity, these results show that acute activation of GFRAL+ neurons causes PR:PROJECT_SUMMARY hypothermia and hyperglycemia. PR:INSTITUTE University of Gothenburg PR:LAST_NAME Ruud PR:FIRST_NAME Johan PR:ADDRESS Medicinaregatan 11 PR:EMAIL johan.ruud@gu.se PR:PHONE +46766186879 #STUDY ST:STUDY_TITLE Activation of GFRAL+ Neurons Induces Hypothermia and Glucoregulatory Responses ST:STUDY_TITLE Associated with Nausea and Torpor ST:STUDY_SUMMARY GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity ST:STUDY_SUMMARY treatment and may mediate metformin effects by long-term GDF15-GFRAL agonism. If ST:STUDY_SUMMARY GFRAL+ neurons acutely regulate glucose and energy homeostasis is however ST:STUDY_SUMMARY underexplored. Here, we report that cell-specific activation of GFRAL+ neurons ST:STUDY_SUMMARY using a variety of techniques causes a torpor-like state, including hypothermia, ST:STUDY_SUMMARY the release of stress hormones, a shift from glucose to lipid oxidation, and ST:STUDY_SUMMARY impaired insulin sensitivity, glucose tolerance and skeletal muscle glucose ST:STUDY_SUMMARY uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of ST:STUDY_SUMMARY blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, ST:STUDY_SUMMARY insulin signaling, adipose tissue differentiation and mitogenesis, and energy ST:STUDY_SUMMARY fluxes. Our findings reveal that acute GFRAL+ neuron activation induces ST:STUDY_SUMMARY endocrine and gluco- and thermoregulatory responses associated with nausea and ST:STUDY_SUMMARY torpor. While chronic activation of GFRAL signaling promotes weight loss in ST:STUDY_SUMMARY obesity, these results show that acute activation of GFRAL+ neurons causes ST:STUDY_SUMMARY hypothermia and hyperglycemia. ST:INSTITUTE University of Gothenburg ST:LAST_NAME Ruud ST:FIRST_NAME Johan ST:ADDRESS Medicinaregatan 11 ST:EMAIL johan.ruud@gu.se ST:PHONE +46766186879 #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 blood1_cage1 2 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=2 SUBJECT_SAMPLE_FACTORS blood1_cage3 4 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=4 SUBJECT_SAMPLE_FACTORS blood1_cage4 6 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=6 SUBJECT_SAMPLE_FACTORS blood1_cage5 8 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=8 SUBJECT_SAMPLE_FACTORS blood1_cage6 10 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=10 SUBJECT_SAMPLE_FACTORS blood1_cage8 12 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=12 SUBJECT_SAMPLE_FACTORS blood1_cage9 14 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=14 SUBJECT_SAMPLE_FACTORS blood1_cage10 16 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=16 SUBJECT_SAMPLE_FACTORS blood1_cage13 18 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=18 SUBJECT_SAMPLE_FACTORS blood1_cage14 20 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=20 SUBJECT_SAMPLE_FACTORS blood1_cage16 22 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=22 SUBJECT_SAMPLE_FACTORS blood1_cage18 24 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=24 SUBJECT_SAMPLE_FACTORS blood1_cage21 26 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=26 SUBJECT_SAMPLE_FACTORS blood1_cage22 28 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=28 SUBJECT_SAMPLE_FACTORS blood1_cage24 30 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=30 SUBJECT_SAMPLE_FACTORS blood1_cage25 32 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=32 SUBJECT_SAMPLE_FACTORS 1.1inca 34 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=34 SUBJECT_SAMPLE_FACTORS 1.2inca 36 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=36 SUBJECT_SAMPLE_FACTORS 1.3inca 38 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=38 SUBJECT_SAMPLE_FACTORS 1.4inca 40 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=40 SUBJECT_SAMPLE_FACTORS 1.5inca 42 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=42 SUBJECT_SAMPLE_FACTORS 1.6inca 44 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=44 SUBJECT_SAMPLE_FACTORS 1.7inca 46 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=46 SUBJECT_SAMPLE_FACTORS 1.8inca 48 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=48 SUBJECT_SAMPLE_FACTORS 2.1inca 50 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=50 SUBJECT_SAMPLE_FACTORS 2.2inca 52 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=52 SUBJECT_SAMPLE_FACTORS 2.3inca 54 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=54 SUBJECT_SAMPLE_FACTORS 2.4inca 56 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=56 SUBJECT_SAMPLE_FACTORS 2.5inca 58 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=58 SUBJECT_SAMPLE_FACTORS 2.6inca 60 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=60 SUBJECT_SAMPLE_FACTORS 2.7inca 62 Sample source:Plasma | Genotype:Transgenic Treatment=CNO_6h; RAW_FILE_NAME=62 SUBJECT_SAMPLE_FACTORS 2.8inca 64 Sample source:Plasma | Genotype:Wild-type Treatment=CNO_6h; RAW_FILE_NAME=64 #COLLECTION CO:COLLECTION_SUMMARY Blood was collected in EDTA-coated tubes, and plasma was obtained through CO:COLLECTION_SUMMARY centrifugation (7000 x g, 7 min, 4°C), snap frozen in liquid nitrogen and CO:COLLECTION_SUMMARY stored at -80°C until further use. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY Control mice (wild-type) and mice expressing hM3Dq in GFRAL neurons (transgenic) TR:TREATMENT_SUMMARY were given CNO (1 mg/kg) i.p. and bled 6 hours later for NMR metabolomics. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Plasma was thawed at room temperature for 15 min before transferring 150 µl to SP:SAMPLEPREP_SUMMARY pre-washed ultrafiltration tubes (Amicon Ultra 0.5 ml, 3k MWCO, Merck Millipore) SP:SAMPLEPREP_SUMMARY which were spun at 14000 x g, at 4°C for 90 min. 90 µl of each filtrate was SP:SAMPLEPREP_SUMMARY mixed with 90 µl buffer (75 mM sodium phosphate pH 7.4, 0.1% w/v sodium azide, SP:SAMPLEPREP_SUMMARY 3.66 mM 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid (TSPd4), in 20% v/v D2O) and SP:SAMPLEPREP_SUMMARY transferred to 3 mm SampleJet NMR-tubes. #ANALYSIS AN:ANALYSIS_TYPE NMR #NMR NM:INSTRUMENT_NAME Bruker Neo NM:INSTRUMENT_TYPE FT-NMR NM:NMR_EXPERIMENT_TYPE 1D-1H NM:SPECTROMETER_FREQUENCY 599.75 MHz #NMR_METABOLITE_DATA NMR_METABOLITE_DATA:UNITS mM NMR_METABOLITE_DATA_START Samples 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 Factors Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type Sample source:Plasma | Genotype:Transgenic Sample source:Plasma | Genotype:Wild-type 2-hydroxybutyrate 00034 00144 0004 00034 00026 00112 00038 0017 00086 00136 00028 00096 00032 0016 00146 00034 00058 00282 00056 00266 005 00068 00274 0011 00058 0023 00192 00068 0012 00038 00244 00038 2-Hydroxyisobutyrate 0007 00106 00102 00074 00096 00076 00086 00086 00114 0011 00068 00078 00086 0012 00108 0008 00096 00146 00076 00176 00132 0008 00116 00086 00098 00104 00096 00082 00126 0009 00138 00076 2-Hydroxyisovalerate 00088 00096 001 00066 00066 00086 00088 00088 00086 001 00068 001 00086 00112 00104 0007 0005 00104 00074 00124 0011 00068 00124 00054 00072 001 0009 0007 00096 0006 00104 00056 2-Oxoisocaproate 00034 00048 00042 0004 00046 00042 0004 00054 00028 00034 00026 00036 0004 00038 00022 0004 00066 00062 00046 00056 00034 00042 00036 00048 00028 00036 0003 00034 0002 00026 0003 00032 3-Hydroxybutyrate 00586 02224 00842 00632 01114 01878 00692 02372 01346 04044 00474 02278 00622 01702 03046 01092 0115 01612 0082 02588 01056 00528 01336 00538 00434 01052 0083 0059 00764 00486 0082 00154 3-Hydroxyisobutyrate 002 00418 00238 00132 00256 00408 0018 0036 00332 00404 00126 00386 00164 0043 00404 00238 003 0053 0024 00636 00416 00252 00448 00236 00164 00456 0036 00224 00302 00148 00276 00162 3-Methyl-2-oxovalerate 00024 00038 00014 00024 0002 00022 00026 00026 00018 0002 00014 00028 00028 00026 00026 0002 00038 0005 00036 0004 00044 0002 00026 00022 00008 0002 00024 00016 00022 00014 00026 00016 Acetate 01818 02834 01662 01654 02116 03164 01602 01844 02412 0206 02072 02698 02124 02048 0157 01298 04282 02266 01838 02146 02378 01898 04542 01064 03656 01656 02526 02466 0341 02894 03372 04404 Acetoacetate 00064 00138 0008 0005 00106 00206 0003 00228 00096 00348 00046 00228 0003 00202 0021 00068 00112 00328 00058 00374 0024 00046 00206 00026 0002 0004 00032 00026 00106 0003 003 00002 Acetone 00056 00156 00054 00056 00048 001 00058 00084 00098 0013 00066 00114 0006 00092 00112 00054 00088 00194 00072 0023 00118 001 00162 00046 001 00078 00086 00068 00124 00074 00138 00306 Alanine 03826 03186 03546 03178 03388 02336 03682 0245 0257 02554 03026 02482 0245 02416 02342 03094 03478 0289 0465 02514 02802 03244 02406 05656 03458 0378 0354 04716 02258 03254 02414 03102 Betaine 0044 0042 00322 00366 00636 00438 00398 0044 00462 00446 00392 00602 0044 00388 00596 00604 00536 00628 00522 00684 00456 0044 00524 00534 0038 0103 00576 00352 0054 00398 00502 00428 Butyrate 00066 00046 00052 00044 0005 00058 00052 00066 00032 00046 00032 00042 00048 0005 00044 00038 0007 00064 00056 0007 00072 00046 00056 00034 00036 00052 0004 00036 0003 0002 00034 00024 Carnitine 0023 00174 00288 00238 00244 00162 00252 00252 00252 00184 00252 00178 00242 00166 00122 0029 00252 00156 00282 00178 00146 00252 00276 00386 0023 00154 00198 00252 00174 0019 00194 00214 Citrate 03308 02734 02966 02358 0251 02012 02778 02244 02218 0212 03052 01882 02554 02248 02216 02726 02674 01896 02906 02006 0247 02438 0155 03656 02598 01952 01826 02554 01788 01886 01432 02412 Creatine 01034 01174 00958 0107 02208 01164 01062 01054 00848 01292 01004 01062 00944 01004 00988 01148 01024 01094 00992 01058 01412 00964 01678 014 01008 01586 01306 01168 01148 00872 01536 01106 Creatinine 00104 00072 0006 00054 00038 00042 00092 00092 0007 0008 00064 00062 00058 00132 0008 00084 00128 00078 00136 00086 00138 00082 00126 001 00082 00094 0009 0012 00086 00076 00078 00116 Dimethylamine 0045 05754 0271 03424 00312 02452 0697 0045 03168 07068 08268 03098 0169 10446 04708 003 00062 03064 01662 03388 1154 02092 0797 00102 03722 07164 01796 0052 04978 02116 07938 0799 Dimethyl sulfone 13676 0749 17508 17782 13272 10914 23174 0512 06618 05956 10852 06928 12294 03136 05134 15792 16268 03702 1638 03974 02854 13706 04712 14978 15386 04068 06544 13302 0399 127 02818 12302 Ethanol 40412 185696 84988 77224 273216 179132 11192 130248 189362 10587 99732 122702 66864 12603 21929 161726 104052 155448 63714 190384 86302 10565 151164 38428 55246 3863 45144 35446 37376 52032 38258 16452 Formate 00924 01004 00942 00956 01466 01066 00924 00854 00972 01096 0093 01074 00922 01108 00952 01014 0177 02018 01408 01678 01634 01436 01738 0134 01664 01778 01772 01602 01518 01652 0202 02644 Fumarate 00072 0007 00074 00062 00076 00062 00092 00054 0006 00056 00066 00052 00082 00032 00054 00082 0004 00024 00064 00038 0003 00058 00024 00142 00046 00048 00036 00064 00028 0003 00014 00036 Glucose 121398 1339 120634 105154 105188 118576 125102 11704 102124 117274 97412 110458 112012 123902 104128 11388 141778 141654 14322 136776 124554 157656 130242 191574 175116 174204 16752 150828 169882 162382 146038 14141 Glutamine 0513 04318 04526 0426 03992 0325 0502 0323 03342 03316 03936 03676 04762 02994 03188 04608 04482 02694 05044 02932 0291 04244 02574 0522 04298 03348 03492 04204 02456 03986 02264 04438 Glycerol 05026 05628 04954 05904 0942 05312 0732 0521 05136 05044 05314 04902 05262 06784 06358 06248 08758 07028 12364 08588 05976 06806 09696 07304 09826 06198 02752 03396 02268 0205 02158 04218 Glycine 01796 01306 01898 01646 01572 00996 0161 01028 01094 01186 01368 01286 01666 01448 0129 01822 01962 0114 02272 01248 01224 014 01052 02444 01616 01456 01312 01964 0105 01688 01472 01704 Histidine 00528 0054 00494 00428 00298 00444 00518 00494 00414 00552 00392 00508 00492 00576 0045 0053 00692 00556 00696 0061 00678 00522 00546 00706 0057 00646 00538 00578 00462 005 0056 00574 Isoleucine 00664 01058 00642 00572 00516 00814 0066 01034 00858 01258 00532 0093 00676 0116 01114 00538 00794 01184 0078 01018 01248 00606 0093 00768 00582 01218 00976 0066 009 00566 01336 00474 Isopropanol 02488 1265 05 0449 17776 09596 06724 08 11918 06704 05716 07624 03822 07808 13852 0993 02162 02558 00972 04322 01566 01496 0289 0058 00778 00872 00732 00662 00796 00748 08576 05834 Lactate 5386 52926 37478 41018 58896 38516 56734 44024 40272 34474 49386 33342 52132 37824 37606 47996 4532 285 59508 28688 27558 51754 247 75194 29182 39956 33466 41276 1797 22824 1276 27094 Leucine 01116 01864 01094 00928 009 01476 01064 01736 01472 0227 0083 01634 01146 02076 01916 00906 0127 01974 01278 01862 02068 0098 01708 01172 00924 02084 01578 0125 01422 00942 02178 0081 Lysine 01728 01108 01498 011 01696 00952 015 01396 0121 01606 01166 0152 01406 01602 01322 01412 01896 01664 01686 01216 01416 01306 01138 01998 01362 01676 01442 01734 01222 01266 01544 01676 Malate 00674 00432 0053 00494 00548 00338 00614 00396 00284 00306 00348 00472 00486 00264 0037 00466 00696 00144 00614 00254 00146 00412 00392 01386 00228 00258 00222 00622 00184 00262 00148 00218 Methanol 0037 00332 00134 00238 00392 00298 00324 00404 0021 0039 00386 00486 00522 00448 00434 0036 00364 00364 0035 00322 00212 00284 00134 00358 00324 0028 00292 00354 00262 00266 00214 00208 Methionine 00408 00294 00402 0033 00384 00246 00368 00266 00238 00318 00304 00292 00364 00286 003 004 00406 00344 00362 0033 00382 00354 0035 00482 00334 00404 00342 00588 0025 0034 00322 00364 Phenylalanine 00546 00744 00466 00382 0044 00572 00542 0066 00614 0082 0037 00622 0044 00786 007 00534 00706 00812 00638 00932 00792 00558 0076 0066 00476 01012 00756 00614 00618 00496 00762 00482 Proline 00498 00242 0042 00374 00522 00256 0042 00392 00206 00374 00348 00392 00554 00456 00352 0053 00824 00424 0072 00344 0028 00496 00392 0075 00356 00502 0045 00846 00282 00312 0036 00398 Propionate 00036 00022 00046 00042 0006 00056 00026 00052 00044 00044 00022 00032 0004 0005 0004 00038 00044 00042 00038 00024 0003 00036 00052 00062 00038 00034 0003 0003 00038 0002 00034 0002 Pyruvate 0198 01564 018 0182 01988 01502 02252 01566 01392 01086 01654 01214 0182 01124 00934 01634 0145 01132 01708 0111 0097 01586 00726 0163 00952 01098 00826 01394 00564 0088 00466 01332 Sarcosine 0008 00058 00064 0006 00096 00134 00088 00078 00078 00068 00078 001 0007 00066 0006 0008 00126 0014 00128 00154 00088 00106 00102 00124 00128 00162 00144 00146 00114 0011 001 00168 Serine 0128 01092 01124 01216 0119 0117 0087 00648 01072 00952 00822 00496 00862 01072 00856 01422 01488 01052 01212 0163 01344 01134 02126 01326 01166 01814 01156 01586 01078 01042 01534 00984 Succinate 003 00494 00288 00264 00314 0021 00414 00226 00204 00338 00314 00352 00448 00248 00454 00558 00314 00136 00624 002 00134 00272 00104 01966 00216 00464 0024 00398 00098 00142 00058 00136 Taurine 06124 11668 03522 03952 06182 05834 03892 06124 04482 07166 03776 05398 03474 0792 06562 04422 06916 15278 06124 14078 07956 04906 08754 06124 05562 14232 12536 06124 0857 03704 11972 04716 Threonine 01016 00672 00878 00792 00538 00862 00476 0053 00614 00594 00626 00568 01002 01158 00726 00696 01296 00906 01414 0052 01026 00922 00398 01104 00932 00772 00706 009 00876 0072 0058 0098 Tyrosine 00654 0055 00704 00586 00618 00502 00772 00486 00476 00586 0049 0051 00594 00568 0054 00872 00764 0055 00808 00566 00568 007 00512 01046 00614 00804 00562 00988 0046 00722 00548 00762 Urea 28512 34904 27938 21198 33054 21878 2658 2279 28214 31298 28456 29516 22272 38348 28238 30638 3525 27782 28434 29388 31842 26146 28722 27788 28082 35388 25668 3422 3246 30704 29686 25148 Uridine 00072 00078 00038 00042 00066 00058 0005 00054 00046 00068 00048 00052 00052 00036 00062 0005 0005 00036 00092 0002 0002 00078 00048 00144 00086 00078 00076 00102 00028 00106 00028 00038 Valerate 0003 00012 00026 00014 00008 0002 00024 00016 00016 00024 00012 00024 00016 00036 00024 00026 00186 00242 00152 00266 0028 00218 00114 0009 00108 00076 00096 0006 00064 00096 00038 00022 Valine 01404 02358 01442 01272 01108 0165 01434 02446 0187 02636 0112 02164 01516 02628 0247 0127 01666 02538 01754 02298 02772 01366 0229 01682 01264 02618 02188 01562 02018 01198 02732 0119 NMR_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name 2-hydroxybutyrate 2-Hydroxyisobutyrate 2-Hydroxyisovalerate 2-Oxoisocaproate 3-Hydroxybutyrate 3-Hydroxyisobutyrate 3-Methyl-2-oxovalerate Acetate Acetoacetate Acetone Alanine Betaine Butyrate Carnitine Citrate Creatine Creatinine Dimethylamine Dimethyl sulfone Ethanol Formate Fumarate Glucose Glutamine Glycerol Glycine Histidine Isoleucine Isopropanol Lactate Leucine Lysine Malate Methanol Methionine Phenylalanine Proline Propionate Pyruvate Sarcosine Serine Succinate Taurine Threonine Tyrosine Urea Uridine Valerate Valine METABOLITES_END #END