#METABOLOMICS WORKBENCH ktsumem_20250507_214726 DATATRACK_ID:5895 STUDY_ID:ST003923 ANALYSIS_ID:AN006440 PROJECT_ID:PR002456 VERSION 1 CREATED_ON May 19, 2025, 7:42 pm #PROJECT PR:PROJECT_TITLE Sex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid PR:PROJECT_TITLE synthesis in mice PR:PROJECT_SUMMARY Brown adipose tissue (BAT), a thermogenic tissue that plays an important role in PR:PROJECT_SUMMARY systemic energy expenditure, has histological and functional sex differences. PR:PROJECT_SUMMARY BAT thermogenic activity is higher in female mice than in male mice. However, PR:PROJECT_SUMMARY the molecular mechanism underlying this functional sex difference has not been PR:PROJECT_SUMMARY fully elucidated. Herein, we demonstrate the role and mechanism of PGC-1α in PR:PROJECT_SUMMARY this sex difference. Inducible adipocyte-specific PGC-1α knockout (KO) mice PR:PROJECT_SUMMARY display mitochondrial morphological defects and decreased BAT thermogenesis only PR:PROJECT_SUMMARY in females. Expression of carbohydrate response-element binding protein beta PR:PROJECT_SUMMARY (Chrebpβ) and its downstream de novo lipogenesis (DNL)-related genes are both PR:PROJECT_SUMMARY reduced only in female KO mice. BAT-specific knockdown of ChREBPβ displays PR:PROJECT_SUMMARY decreased DNL-related gene expression and mitochondrial morphological defects PR:PROJECT_SUMMARY followed by reduced BAT thermogenesis in female wild-type mice. Lipidomics PR:PROJECT_SUMMARY reveals that, PGC-1α increases ether-linked phosphatidylethanolamine (PE) and PR:PROJECT_SUMMARY cardiolipin(18:2)₄ levels through Chrebpβ-dependent and -independent PR:PROJECT_SUMMARY mechanisms in female BAT. Furthermore, PGC-1α enhances the sensitivity of PR:PROJECT_SUMMARY female BAT estrogen signaling, thereby increasing Chrebpβ and its downstream PR:PROJECT_SUMMARY DNL-related gene expression. These findings demonstrate that PGC-1α–mediated PR:PROJECT_SUMMARY phospholipid synthesis plays a pivotal role in BAT thermogenesis in a PR:PROJECT_SUMMARY sex-dependent manner. PR:INSTITUTE Institute of Science Tokyo PR:LAST_NAME Tsujimoto PR:FIRST_NAME Kazutaka PR:ADDRESS 1-5-45 Yushima, Bunkyo-ku, Tokyo, Tokyo, 113-8510, Japan PR:EMAIL ktsumem@tmd.ac.jp PR:PHONE +81-3-5803-5216 #STUDY ST:STUDY_TITLE Sex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid ST:STUDY_TITLE synthesis in mice ST:STUDY_SUMMARY Brown adipose tissue (BAT), a thermogenic tissue that plays an important role in ST:STUDY_SUMMARY systemic energy expenditure, has histological and functional sex differences. ST:STUDY_SUMMARY BAT thermogenic activity is higher in female mice than in male mice. However, ST:STUDY_SUMMARY the molecular mechanism underlying this functional sex difference has not been ST:STUDY_SUMMARY fully elucidated. Herein, we demonstrate the role and mechanism of PGC-1α in ST:STUDY_SUMMARY this sex difference. Inducible adipocyte-specific PGC-1α knockout (KO) mice ST:STUDY_SUMMARY display mitochondrial morphological defects and decreased BAT thermogenesis only ST:STUDY_SUMMARY in females. Expression of carbohydrate response-element binding protein beta ST:STUDY_SUMMARY (Chrebpβ) and its downstream de novo lipogenesis (DNL)-related genes are both ST:STUDY_SUMMARY reduced only in female KO mice. BAT-specific knockdown of ChREBPβ displays ST:STUDY_SUMMARY decreased DNL-related gene expression and mitochondrial morphological defects ST:STUDY_SUMMARY followed by reduced BAT thermogenesis in female wild-type mice. Lipidomics ST:STUDY_SUMMARY reveals that, PGC-1α increases ether-linked phosphatidylethanolamine (PE) and ST:STUDY_SUMMARY cardiolipin(18:2)₄ levels through Chrebpβ-dependent and -independent ST:STUDY_SUMMARY mechanisms in female BAT. Furthermore, PGC-1α enhances the sensitivity of ST:STUDY_SUMMARY female BAT estrogen signaling, thereby increasing Chrebpβ and its downstream ST:STUDY_SUMMARY DNL-related gene expression. These findings demonstrate that PGC-1α–mediated ST:STUDY_SUMMARY phospholipid synthesis plays a pivotal role in BAT thermogenesis in a ST:STUDY_SUMMARY sex-dependent manner. ST:INSTITUTE Institute of Science Tokyo ST:LAST_NAME Tsujimoto ST:FIRST_NAME Kazutaka ST:ADDRESS 1-5-45 Yushima, Bunkyo-ku, Tokyo, Tokyo, 113-8510, Japan ST:EMAIL ktsumem@tmd.ac.jp ST:PHONE +81-3-5803-5216 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENDER Male and female #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 - M1 Sample source:BAT | Sex:Male | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_001_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_001_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_001_d3.mzML SUBJECT_SAMPLE_FACTORS - M2 Sample source:BAT | Sex:Male | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_002_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_002_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_002_d3.mzML SUBJECT_SAMPLE_FACTORS - M3 Sample source:BAT | Sex:Male | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_003_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_003_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_003_d3.mzML SUBJECT_SAMPLE_FACTORS - M4 Sample source:BAT | Sex:Male | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_004_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_004_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_004_d3.mzML SUBJECT_SAMPLE_FACTORS - M5 Sample source:BAT | Sex:Male | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_005_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_005_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_005_d3.mzML SUBJECT_SAMPLE_FACTORS - MC1 Sample source:BAT | Sex:Male | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_006_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_006_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_006_d3.mzML SUBJECT_SAMPLE_FACTORS - MC2 Sample source:BAT | Sex:Male | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_007_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_007_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_007_d3.mzML SUBJECT_SAMPLE_FACTORS - MC3 Sample source:BAT | Sex:Male | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_008_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_008_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_008_d3.mzML SUBJECT_SAMPLE_FACTORS - MC4 Sample source:BAT | Sex:Male | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_009_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_009_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_009_d3.mzML SUBJECT_SAMPLE_FACTORS - MC5 Sample source:BAT | Sex:Male | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_010_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_010_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_010_d3.mzML SUBJECT_SAMPLE_FACTORS - F1 Sample source:BAT | Sex:Female | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_011_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_011_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_011_d3.mzML SUBJECT_SAMPLE_FACTORS - F2 Sample source:BAT | Sex:Female | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_012_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_012_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_012_d3.mzML SUBJECT_SAMPLE_FACTORS - F3 Sample source:BAT | Sex:Female | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_013_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_013_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_013_d3.mzML SUBJECT_SAMPLE_FACTORS - F4 Sample source:BAT | Sex:Female | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_014_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_014_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_014_d3.mzML SUBJECT_SAMPLE_FACTORS - F5 Sample source:BAT | Sex:Female | Genotype:Control RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_015_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_015_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_015_d3.mzML SUBJECT_SAMPLE_FACTORS - FC1 Sample source:BAT | Sex:Female | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_016_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_016_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_016_d3.mzML SUBJECT_SAMPLE_FACTORS - FC2 Sample source:BAT | Sex:Female | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_017_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_017_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_017_d3.mzML SUBJECT_SAMPLE_FACTORS - FC3 Sample source:BAT | Sex:Female | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_018_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_018_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_018_d3.mzML SUBJECT_SAMPLE_FACTORS - FC4 Sample source:BAT | Sex:Female | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_019_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_019_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_019_d3.mzML SUBJECT_SAMPLE_FACTORS - FC5 Sample source:BAT | Sex:Female | Genotype:KO RAW_FILE_NAME(Raw Data File Name C)=TMDUM030-1_C_20220315_020_d1.mzML; RAW_FILE_NAME(Raw Data File Name O)=TMDUM030-1_O_20220310_020_d3.mzML; RAW_FILE_NAME(Raw Data File Name S)=TMDUM030-1_S_20220310_020_d3.mzML #COLLECTION CO:COLLECTION_SUMMARY All mice were treated with norepinephrine (NE) and exposed to a warm environment CO:COLLECTION_SUMMARY (33°C) for 30 minutes prior to tissue collection, to evaluate brown adipose CO:COLLECTION_SUMMARY tissue (BAT) metabolism under conditions of maximal oxygen consumption. Tissues CO:COLLECTION_SUMMARY were collected from mice following euthanasia. Brown adipose tissue was isolated CO:COLLECTION_SUMMARY and immediately frozen in liquid nitrogen before being stored at -80°C for CO:COLLECTION_SUMMARY later analysis. CO:SAMPLE_TYPE Brown adipose tissue #TREATMENT TR:TREATMENT_SUMMARY Tamoxifen-inducible adipocyte-specific PGC-1α knockout (KO) mice were generated TR:TREATMENT_SUMMARY by crossing Pgc1a flox/flox mice (JAX stock #009666) with Adipoq-CreERT2 mice TR:TREATMENT_SUMMARY (JAX stock #025124). Eight-week-old male and female KO and floxed Control mice TR:TREATMENT_SUMMARY were injected intraperitoneally with tamoxifen (100 mg/kg) for 5 consecutive TR:TREATMENT_SUMMARY days and analyzed at least 8 weeks after the last injection. All mice were TR:TREATMENT_SUMMARY maintained at 30°C for one week before NE injection and tissue sampling. At the TR:TREATMENT_SUMMARY time of sacrifice, mice were placed at 33°C and injected with norepinephrine TR:TREATMENT_SUMMARY (NE, 1 mg/kg, i.p.). Thirty minutes after NE administration, brown adipose TR:TREATMENT_SUMMARY tissue (BAT) was collected for metabolomic analysis. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Approximately 25–30 mg of frozen BAT was homogenized with zirconia beads in SP:SAMPLEPREP_SUMMARY 50% acetonitrile containing internal standards. After centrifugation, the SP:SAMPLEPREP_SUMMARY aqueous layer was filtered through a 5-kDa cutoff filter, dried under vacuum, SP:SAMPLEPREP_SUMMARY and reconstituted in Milli-Q water for metabolomic analysis. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Fused silica capillary (50 μm i.d. × 80 cm). H3301-1001 (for cation analysis) CH:CHROMATOGRAPHY_SUMMARY and H3302-1021 (for anion analysis) are commercial electrophoresis buffers CH:CHROMATOGRAPHY_SUMMARY provided by Human Metabolome Technologies (HMT). H3301-1001 is optimized for the CH:CHROMATOGRAPHY_SUMMARY separation of cationic metabolites such as amino acids and polyamines, typically CH:CHROMATOGRAPHY_SUMMARY under slightly acidic conditions. H3302-1021 is designed for the separation of CH:CHROMATOGRAPHY_SUMMARY anionic metabolites such as organic acids and phosphorylated compounds, under CH:CHROMATOGRAPHY_SUMMARY basic conditions. CH:CHROMATOGRAPHY_TYPE CE CH:INSTRUMENT_NAME Agilent 7100 CE CH:COLUMN_NAME Agilent Fused silica capillary (80cm x 50um) CH:SOLVENT_A HMT electrophoresis buffer H3301-1001 CH:SOLVENT_B N/A CH:FLOW_GRADIENT N/A CH:FLOW_RATE N/A CH:COLUMN_TEMPERATURE N/A #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6230 TOF MS:INSTRUMENT_TYPE TOF MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS CE-TOFMS in positive ion mode (m/z 50–1000). Peaks extracted using MasterHands MS:MS_COMMENTS and MassHunter (Agilent) and annotated based on m/z and migration time using HMT MS:MS_COMMENTS metabolite database. #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS arbitrary unit MS_METABOLITE_DATA_START Samples M1 M2 M3 M4 M5 MC1 MC2 MC3 MC4 MC5 F1 F2 F3 F4 F5 FC1 FC2 FC3 FC4 FC5 Factors Sample source:BAT | Sex:Male | Genotype:Control Sample source:BAT | Sex:Male | Genotype:Control Sample source:BAT | Sex:Male | Genotype:Control Sample source:BAT | Sex:Male | Genotype:Control Sample source:BAT | Sex:Male | Genotype:Control Sample source:BAT | Sex:Male | Genotype:KO Sample source:BAT | Sex:Male | Genotype:KO Sample source:BAT | Sex:Male | Genotype:KO Sample source:BAT | Sex:Male | Genotype:KO Sample source:BAT | Sex:Male | Genotype:KO Sample source:BAT | Sex:Female | Genotype:Control Sample source:BAT | Sex:Female | Genotype:Control Sample source:BAT | Sex:Female | Genotype:Control Sample source:BAT | Sex:Female | Genotype:Control Sample source:BAT | Sex:Female | Genotype:Control Sample source:BAT | Sex:Female | Genotype:KO Sample source:BAT | Sex:Female | Genotype:KO Sample source:BAT | Sex:Female | Genotype:KO Sample source:BAT | Sex:Female | Genotype:KO Sample source:BAT | Sex:Female | Genotype:KO Gly 353 419 434 508 528 363 445 299 530 459 463 591 426 679 484 473 451 473 396 575 Putrescine 0.8 0.2 0.4 N.D. 1.3 N.D. 0.4 0.4 2.1 0.6 0.9 1.1 5.2 1.5 0.2 2.4 1.3 0.3 0.14 1.7 Sarcosine 2 N.D. N.D. N.D. 2.1 N.D. 1.8 N.D. 1.8 N.D. N.D. N.D. 0.2 N.D. 0.7 N.D. N.D. N.D. N.D. N.D. Ala 659 767 673 765 770 769 1306 909 1177 1076 1057 912 993 673 989 695 1024 674 609 888 β-Ala 7.8 9.4 11 10 13 7.1 12 5.4 13 12 4.8 5.9 4.7 6.5 4.9 5.1 3.4 5.7 3.5 5.1 N,N-Dimethylglycine N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. γ-Aminobutyric acid 0.9 3.9 1.4 3.5 2 0.7 3.9 2.2 1.9 2.3 2.2 7.5 2 1 1.4 N.D. N.D. N.D. 0.6 N.D. Choline 162 181 177 51 105 156 116 80 81 88 111 78 109 117 98 38 50 49 105 63 Ser 148 252 178 328 206 163 179 159 213 175 148 252 202 187 190 192 181 168 138 193 Carnosine N.D. 0.5 2 N.D. 2 1.2 2.8 N.D. 2 7 N.D. 2.8 0.11 14 1.4 N.D. 2.4 0.9 0.7 N.D. Creatinine 2.4 2.3 7.2 3.2 3.4 2.4 2.5 3.9 5.1 3.8 3.3 4.2 4.1 6.8 3.1 2.1 2.9 3.1 2.9 3 Pro N.D. N.D. N.D. N.D. 3.3 N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. Val 84 76 97 51 120 88 115 89 127 87 108 70 79 114 86 78 84 102 94 131 Betaine 532 519 318 527 434 227 379 360 222 289 238 750 533 383 406 227 382 322 227 294 Thr 131 191 146 220 188 143 186 147 207 143 121 173 202 145 158 150 187 122 122 172 Homoserine N.D. N.D. N.D. 1.2 N.D. N.D. N.D. N.D. 0.09 N.D. N.D. N.D. N.D. N.D. N.D. 0.2 N.D. N.D. N.D. N.D. Betaine aldehyde 0.7 0.04 N.D. N.D. N.D. N.D. 0.2 N.D. N.D. N.D. 0.7 0.2 0.5 N.D. 0.8 N.D. N.D. N.D. N.D. N.D. Cys N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. Hydroxyproline 21 13 20 14 28 19 22 11 27 26 12 13 17 20 16 14 12 14 14 15 Creatine 1541 1501 1930 1345 2083 1743 2128 1647 2037 2455 2113 2456 2437 4048 2518 1529 2128 1811 1883 1888 Ile 40 43 52 28 61 40 58 41 56 45 49 37 37 60 46 42 40 57 47 74 Leu 92 92 120 69 135 94 119 96 123 106 109 83 81 116 100 93 97 129 103 162 Asn 21 26 27 52 27 23 36 25 41 29 29 39 28 49 33 46 38 43 31 59 Ornithine 5.9 7.3 5.2 6.5 6.1 6.8 6.7 5.3 7.3 5.1 5 7 9.1 7.1 5.5 5 5.4 4.8 5.6 4.7 Asp 249 206 293 162 303 262 223 187 223 191 235 265 318 240 167 221 172 207 225 210 Homocysteine N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. N.D. Adenine 1.5 1.3 1.8 2.7 1.9 1.4 2.2 1.7 2.9 2 2.3 1.9 2 2.1 2.1 2.6 2.5 2.3 1.5 3.6 Hypoxanthine 18 19 17 10 25 22 19 13 18 23 28 21 21 23 20 18 26 18 24 30 Spermidine 23 30 23 28 24 15 25 24 26 24 24 38 31 28 35 27 29 25 19 29 Gln 872 1762 907 2919 1157 814 997 1004 927 845 1142 2158 931 1231 1222 1276 1213 940 754 1128 Lys 88 100 94 96 103 82 114 74 96 100 88 134 102 214 132 126 131 127 83 117 Glu 560 695 1520 487 956 829 705 484 665 510 968 683 525 1123 702 557 541 622 566 681 Met 26 24 33 25 39 25 31 24 33 29 29 24 30 32 27 25 29 32 26 35 Guanine N.D. 0.15 N.D. N.D. N.D. N.D. N.D. 0.3 0.05 N.D. N.D. 0.07 N.D. 0.3 N.D. N.D. N.D. 0.4 0.03 0.05 His 37 61 42 58 50 36 44 39 45 40 46 97 39 63 50 38 47 48 38 39 Carnitine 874 1112 970 1278 1141 804 1039 643 809 831 1154 1136 1033 1276 1525 1263 1158 1406 899 1417 Phe 42 49 43 43 50 34 43 36 48 40 49 50 42 54 46 43 47 52 37 61 Arg 40 49 45 53 47 44 52 34 52 48 44 52 47 81 57 51 51 52 44 54 Citrulline 41 68 42 102 50 42 52 47 53 51 40 69 58 51 46 49 53 34 38 41 Tyr 49 53 37 48 70 26 40 29 37 41 45 58 39 41 39 30 35 45 32 47 S-Adenosylhomocysteine 2.4 2.5 2.6 1.8 2.6 1.9 2.7 2.2 2.4 2.5 2.9 2.2 2.7 1.8 2 1.6 1.9 2.7 2.4 2.3 Spermine N.D. 1 1.1 2.3 1 N.D. 0.7 0.4 0.6 1.2 N.D. 2.1 1.4 0.7 2.6 1 1.3 N.D. N.D. 0.8 Trp 13 16 13 13 18 12 16 13 19 13 21 17 23 18 16 17 18 16 16 19 Cystathionine 3.6 N.D. N.D. 3.4 N.D. N.D. 3.5 3.6 N.D. 3.8 N.D. N.D. 3.9 3.9 3.7 3.9 4.5 4.3 3.6 4.6 Adenosine 38 49 50 38 62 47 68 50 55 59 44 61 58 43 39 57 57 61 60 70 Inosine 20 22 21 18 28 26 29 14 27 34 43 33 29 37 24 35 46 38 42 60 Guanosine 5.8 8.8 7.2 7.6 8.1 8.4 9.9 8.1 10 12 8.1 7.3 5.3 6 6.1 8.5 9.3 9.5 11 13 Argininosuccinic acid 2.8 3 1.8 1.6 2.5 3.2 2.7 2.6 2.4 2.7 2.4 3.5 3 2.4 2.6 1.8 2.4 1.5 1.8 1.4 Glutathione (GSSG) 389 390 434 225 436 321 440 242 281 305 481 453 529 343 412 275 287 296 270 305 Glutathione (GSH) 323 313 281 505 293 374 436 598 525 394 182 160 268 453 459 472 552 524 492 710 S-Adenosylmethionine 13 14 14 16 13 11 14 15 15 16 15 19 16 18 15 13 17 18 14 19 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Gly Putrescine Sarcosine Ala β-Ala N,N-Dimethylglycine γ-Aminobutyric acid Choline Ser Carnosine Creatinine Pro Val Betaine Thr Homoserine Betaine aldehyde Cys Hydroxyproline Creatine Ile Leu Asn Ornithine Asp Homocysteine Adenine Hypoxanthine Spermidine Gln Lys Glu Met Guanine His Carnitine Phe Arg Citrulline Tyr S-Adenosylhomocysteine Spermine Trp Cystathionine Adenosine Inosine Guanosine Argininosuccinic acid Glutathione (GSSG) Glutathione (GSH) S-Adenosylmethionine METABOLITES_END #END