#METABOLOMICS WORKBENCH t_ktmt_0211_20240805_184830 DATATRACK_ID:5084 STUDY_ID:ST003452 ANALYSIS_ID:AN005669 PROJECT_ID:PR002126 VERSION 1 CREATED_ON August 28, 2024, 10:43 am #PROJECT PR:PROJECT_TITLE Integrative proteomic and lipidomic analysis of GNB1 and SCARB2 knockdown in PR:PROJECT_TITLE human subcutaneous adipocytes PR:PROJECT_TYPE Multi-omics (Proteomics and Lipidomics) PR:PROJECT_SUMMARY This project focuses on the knockdown of two candidate genes, GNB1 and SCARB2, PR:PROJECT_SUMMARY identified through a comprehensive integration of genome-wide association PR:PROJECT_SUMMARY studies (GWAS) related to BMI and proteomics data from previous studies using PR:PROJECT_SUMMARY human subcutaneous adipocytes before and after fat accumulation. We aim to PR:PROJECT_SUMMARY understand the regulatory roles of these genes in fat accumulation by performing PR:PROJECT_SUMMARY an integrated analysis of changes in the proteome and lipidome using mass PR:PROJECT_SUMMARY spectrometry following gene knockdown. PR:INSTITUTE Hamamatsu University School of Medicine PR:LAST_NAME Kitamoto PR:FIRST_NAME Takuya PR:ADDRESS 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Japan PR:EMAIL t.ktmt@hama-med.ac.jp PR:PHONE +81-53-435-2987 #STUDY ST:STUDY_TITLE Integrated Proteomic and Lipidomic Analysis ST:STUDY_SUMMARY GNB1 and SCARB2 genes were knocked down in human subcutaneous adipocytes using ST:STUDY_SUMMARY RNA interference. Both proteomic and lipidomic analyses were performed using ST:STUDY_SUMMARY mass spectrometry. The proteomic results revealed significant changes in the ST:STUDY_SUMMARY expression levels of key proteins involved in lipid metabolism and adipogenesis. ST:STUDY_SUMMARY The lipidomic analysis identified significant changes in lipid species, ST:STUDY_SUMMARY including phosphatidylcholines, ceramides, and cholesterol esters. This ST:STUDY_SUMMARY integrated analysis provides insights into the molecular pathways and lipid ST:STUDY_SUMMARY metabolism regulated by GNB1 and SCARB2 in adipocyte function. ST:INSTITUTE Hamamatsu University School of Medicine ST:LAST_NAME Kitamoto ST:FIRST_NAME Takuya ST:ADDRESS 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Japan ST:EMAIL t.ktmt@hama-med.ac.jp ST:PHONE +81-53-435-2987 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:AGE_OR_AGE_RANGE 38 SU:GENDER Female SU:CELL_BIOSOURCE_OR_SUPPLIER Zen-Bio, Inc. (Research Triangle Park, NC, USA) SU:SUBJECT_COMMENTS The cell line was derived from abdominal subcutaneous adipose tissue #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 NC_1 proteome_nc_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=proteome; RAW_FILE_NAME=proteome_nc_1.raw SUBJECT_SAMPLE_FACTORS NC_2 proteome_nc_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=proteome; RAW_FILE_NAME=proteome_nc_2.raw SUBJECT_SAMPLE_FACTORS NC_3 proteome_nc_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=proteome; RAW_FILE_NAME=proteome_nc_3.raw SUBJECT_SAMPLE_FACTORS GNB1_1 proteome_GNB1_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=proteome; RAW_FILE_NAME=proteome_GNB1_1.raw SUBJECT_SAMPLE_FACTORS GNB1_2 proteome_GNB1_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=proteome; RAW_FILE_NAME=proteome_GNB1_2.raw SUBJECT_SAMPLE_FACTORS GNB1_3 proteome_GNB1_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=proteome; RAW_FILE_NAME=proteome_GNB1_3.raw SUBJECT_SAMPLE_FACTORS SCARB2_1 proteome_SCARB2_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=proteome; RAW_FILE_NAME=proteome_SCARB2_1.raw SUBJECT_SAMPLE_FACTORS SCARB2_2 proteome_SCARB2_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=proteome; RAW_FILE_NAME=proteome_SCARB2_2.raw SUBJECT_SAMPLE_FACTORS SCARB2_3 proteome_SCARB2_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=proteome; RAW_FILE_NAME=proteome_SCARB2_3.raw SUBJECT_SAMPLE_FACTORS NC_1 lipidome_nc_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=lipidome; RAW_FILE_NAME=lipidome_nc_1.raw SUBJECT_SAMPLE_FACTORS NC_2 lipidome_nc_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=lipidome; RAW_FILE_NAME=lipidome_nc_2.raw SUBJECT_SAMPLE_FACTORS NC_3 lipidome_nc_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Analysis Method=lipidome; RAW_FILE_NAME=lipidome_nc_3.raw SUBJECT_SAMPLE_FACTORS GNB1_1 lipidome_GNB1_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_GNB1_1.raw SUBJECT_SAMPLE_FACTORS GNB1_2 lipidome_GNB1_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_GNB1_2.raw SUBJECT_SAMPLE_FACTORS GNB1_3 lipidome_GNB1_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_GNB1_3.raw SUBJECT_SAMPLE_FACTORS SCARB2_1 lipidome_SCARB2_1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_SCARB2_1.raw SUBJECT_SAMPLE_FACTORS SCARB2_2 lipidome_SCARB2_2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_SCARB2_2.raw SUBJECT_SAMPLE_FACTORS SCARB2_3 lipidome_SCARB2_3 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Analysis Method=lipidome; RAW_FILE_NAME=lipidome_SCARB2_3.raw #COLLECTION CO:COLLECTION_SUMMARY Primary cultured human preadipocytes were obtained from Zen-Bio, Inc., derived CO:COLLECTION_SUMMARY from the abdominal subcutaneous adipose tissue of a 38-year-old Caucasian woman. CO:COLLECTION_SUMMARY The cells were grown, differentiated, and collected as mature adipocytes on day CO:COLLECTION_SUMMARY 14. All experiments were performed in three independent replicates. CO:SAMPLE_TYPE White adipose #TREATMENT TR:TREATMENT_SUMMARY siRNA transfection was performed to knock down the expression of GNB1 and SCARB2 TR:TREATMENT_SUMMARY genes in differentiated human subcutaneous adipocytes. Three rounds of TR:TREATMENT_SUMMARY transfection were carried out over a period of 14 days. Following the final TR:TREATMENT_SUMMARY transfection, cells were harvested for both proteomic and lipidomic analyses. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Proteomics: Cells were lysed, proteins were extracted, and concentrations were SP:SAMPLEPREP_SUMMARY determined using the BCA assay. Proteins were precipitated, reduced, alkylated, SP:SAMPLEPREP_SUMMARY and digested with trypsin. Peptides were purified using a MonoSpin C18 column SP:SAMPLEPREP_SUMMARY and analyzed using an EASY-nLC 1200 and a Q-Exactive Orbitrap mass spectrometer SP:SAMPLEPREP_SUMMARY (Thermo Fisher Scientific). Data were processed using Proteome Discoverer 2.2 SP:SAMPLEPREP_SUMMARY software (Thermo Fisher Scientific). Lipidomics: Lipids were extracted using the SP:SAMPLEPREP_SUMMARY Bligh and Dyer method, dissolved in methanol, and analyzed using an Ultimate SP:SAMPLEPREP_SUMMARY 3000 and a Q-Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific). SP:SAMPLEPREP_SUMMARY Data were processed using LipidSearch software version 5.1.9 (Thermo Fisher SP:SAMPLEPREP_SUMMARY Scientific). #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY HPLC lipidome analysis. C18 column (Acclaim 120 C18 column (3 μm, 2.1 mm × 150 CH:CHROMATOGRAPHY_SUMMARY mm), gradient elution with aqueous and organic solvents containing ammonium CH:CHROMATOGRAPHY_SUMMARY formate and formic acid. Flow rate: 300 μL/min, column at 50°C. 70-min CH:CHROMATOGRAPHY_SUMMARY gradient. Solvent A: 5 mM ammonium formate in water/methanol/acetonitrile CH:CHROMATOGRAPHY_SUMMARY (2:1:1) with 0.1% formic acid; Solvent B: 5 mM ammonium formate in CH:CHROMATOGRAPHY_SUMMARY isopropanol/acetonitrile (9:1) with 0.1% formic acid CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Thermo Acclaim (150 x 2.1mm, 3um) CH:SOLVENT_A 50% water/25% methanol/25% acetonitrile; 5 mM ammonium formate; 0.1% formic acid CH:SOLVENT_B 90% isopropanol/10% acetonitrile; 5 mM ammonium formate; 0.1% formic acid CH:FLOW_GRADIENT 20% to 100% B over 50 min, 100% B for 10 min, then return to 20% B CH:FLOW_RATE 300 μL/min CH:COLUMN_TEMPERATURE 50℃ #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS MS acquisition Comments: Full scan MS followed by data-dependent MS/MS Data MS:MS_COMMENTS processing Comments: Raw data processed using LipidSearch for lipidomics MS:MS_COMMENTS Software/procedures used for feature assignments: LipidSearch for lipid MS:MS_COMMENTS identification #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Relative abundance (isotope normalized) MS_METABOLITE_DATA_START Samples lipidome_nc_1 lipidome_nc_2 lipidome_nc_3 lipidome_GNB1_1 lipidome_GNB1_2 lipidome_GNB1_3 lipidome_SCARB2_1 lipidome_SCARB2_2 lipidome_SCARB2_3 Factors Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:Negative Control Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:GNB1 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 Sample source:Human subcutaneous adipocytes | Gene Knockdown Target:SCARB2 LPE(22:4) 0.194415916 0.363313336 0.320963586 0.12129017 0.346302454 0.366870128 0.374226514 0.219531662 0.178661389 PE(15:0_24:5) 0.008770126 0.009927218 0.009036028 0.008601428 0.010132129 0.008114132 0.011669713 0.010352754 0.00983851 PE(16:0_20:4) 0.007813013 0.017717606 0.010938387 0.014409328 0.016914212 0.012346197 0.014337357 0.009674035 0.011805803 PE(16:1_18:1) 0.017140389 0.031425842 0.016153226 0.018102799 0.021299004 0.017719976 0.017425542 0.016611072 0.014040322 PE(18:0_20:4) 0.057151692 0.087431483 0.05652753 0.067334518 0.081590767 0.085270261 0.088636957 0.0846679 0.074307716 PE(18:0_22:3) 0.002804163 0.004356677 0.002583149 0.003874243 0.004176938 0.00529542 0.002797783 0.002711419 0.002321213 PE(18:0_22:4) 0.009634258 0.016496918 0.009933761 0.013002772 0.014367558 0.015586713 0.013127548 0.012128969 0.010309382 PE(18:0_22:5) 0.013532661 0.024220438 0.012711772 0.018047061 0.024207924 0.023000721 0.018972747 0.017463143 0.018658099 PE(18:1_20:4) 0.025951675 0.036566061 0.024569796 0.037359525 0.033829469 0.035588023 0.037195991 0.032966349 0.029134581 PE(O-12:1_20:4) 0.010497537 0.012298542 0.010558476 0.012190805 0.011308057 0.012531612 0.012489507 0.009220173 0.009404015 PE(O-16:1_16:1) 0.015129982 0.027406919 0.014682122 0.013195143 0.014790753 0.015325952 0.012370414 0.012007121 0.010399306 PE(O-16:1_18:1) 0.048397347 0.073602929 0.049852802 0.050664337 0.049782397 0.054053594 0.05151929 0.048851518 0.04321655 PE(O-16:1_20:4) 0.107359621 0.151227057 0.105193986 0.12399295 0.118426642 0.130151346 0.150027112 0.150614425 0.125359104 PE(O-16:1_22:6) 0.015786398 0.022391794 0.016045106 0.021022265 0.019735743 0.022133263 0.023131766 0.023800964 0.018517007 PE(O-17:1_20:4) 0.008122028 0.010446016 0.007581222 0.008893676 0.009762725 0.009159274 0.012288474 0.012773639 0.009817601 PE(O-18:1_18:1) 0.015822653 0.022310369 0.015760523 0.019006658 0.018973261 0.020888423 0.020771996 0.020487737 0.017372975 PE(O-18:1_20:3) 0.014346037 0.022892169 0.013853433 0.020383538 0.019612144 0.022036297 0.018507421 0.01889248 0.01492342 PE(O-18:1_20:4) 0.077460493 0.103554939 0.079534224 0.085729565 0.089795279 0.096413549 0.113182576 0.109657962 0.096391113 PE(O-18:1_22:4) 0.022535241 0.033268133 0.015653629 0.027765057 0.026530186 0.031714604 0.031773542 0.028752657 0.019423054 PE(O-18:1_22:6) 0.013831439 0.019729797 0.014444328 0.01764635 0.015464801 0.017826115 0.019150081 0.01433554 0.014446428 PE(O-18:2_18:1) 0.024085645 0.034193827 0.020924894 0.025711789 0.029087459 0.028289327 0.030480188 0.029376588 0.024675744 PE(O-18:2_20:4) 0.093768527 0.123745082 0.094327621 0.097454129 0.102700021 0.112951582 0.133390236 0.118624587 0.104758019 PE(O-18:2_22:4) 0.033782602 0.044747197 0.0291452 0.034989907 0.033446487 0.039310751 0.044249192 0.039496016 0.029195777 PE(O-18:2_22:5) 0.01260647 0.017938681 0.011498616 0.01343783 0.014447114 0.015489746 0.015717872 0.011102162 0.011266595 PE(O-18:2_22:6) 0.012416668 0.018162258 0.011019171 0.015287277 0.014966402 0.016354583 0.016846143 0.0163036 0.012870621 PI(16:0_16:1) 0.019904332 0.036499222 0.017662218 0.024089106 0.022546122 0.021840194 0.016533365 0.017708447 0.01630706 PI(18:0_18:1) 0.067795199 0.079898911 0.063379977 0.087055397 0.086476334 0.097265694 0.079265263 0.078969297 0.075153374 PI(18:0_20:3) 0.124767473 0.161990669 0.09171214 0.195333994 0.189765423 0.239095258 0.107311879 0.096155945 0.10845378 PI(18:0_22:4) 0.029705908 0.034541991 0.021649468 0.043391374 0.040775524 0.04726097 0.034733791 0.032074302 0.029512842 PI(18:0_22:5) 0.01550093 0.020109642 0.011825058 0.032173132 0.026930462 0.038084214 0.024694747 0.021206289 0.019401581 PS(16:0_16:1) 0.010964077 0.02331129 0.011315653 0.012822987 0.013562669 0.010467319 0.010436943 0.009848198 0.009792429 PS(18:0_22:5) 0.011710944 0.016864462 0.010276351 0.013593278 0.009964272 0.014589903 0.012495821 0.010978497 0.007283643 PS(18:0_22:6) 0.008532999 0.011773012 0.008334329 0.012457191 0.014741696 0.011125064 0.012636051 0.012568938 0.010055279 PS(18:1_18:1) 0.023596491 0.028346142 0.019970135 0.028516143 0.033420722 0.032575661 0.023333024 0.024000891 0.018589471 PS(18:1_20:1) 0.036716792 0.056339589 0.032637678 0.059794306 0.053510042 0.048674339 0.055103083 0.042465601 0.039405477 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name BaseRT MainIon Calculated m/z LPE(22:4) 14.9388 M-H 528.3096 PE(15:0_24:5) 34.1454 M-H 778.5392 PE(16:0_20:4) 33.5383 M-H 738.5079 PE(16:1_18:1) 33.418 M-H 714.5079 PE(18:0_20:4) 35.7498 M-H 766.5392 PE(18:0_22:3) 38.4275 M-H 796.5862 PE(18:0_22:4) 37.1489 M-H 794.5705 PE(18:0_22:5) 35.9561 M-H 792.5549 PE(18:1_20:4) 33.878 M-H 764.5236 PE(O-12:1_20:4) 29.7252 M-H 666.4504 PE(O-16:1_16:1) 34.3329 M-H 672.4974 PE(O-16:1_18:1) 36.421 M-H 700.5287 PE(O-16:1_20:4) 35.0192 M-H 722.513 PE(O-16:1_22:6) 34.2741 M-H 746.513 PE(O-17:1_20:4) 35.7555 M-H 736.5287 PE(O-18:1_18:1) 38.328 M-H 728.56 PE(O-18:1_20:3) 37.9283 M-H 752.56 PE(O-18:1_20:4) 36.6578 M-H 750.5443 PE(O-18:1_22:4) 38.1106 M-H 778.5756 PE(O-18:1_22:6) 36.387 M-H 774.5443 PE(O-18:2_18:1) 36.6043 M-H 726.5443 PE(O-18:2_20:4) 34.9384 M-H 748.5287 PE(O-18:2_22:4) 36.6807 M-H 776.56 PE(O-18:2_22:5) 35.1454 M-H 774.5443 PE(O-18:2_22:6) 34.5053 M-H 772.5287 PI(16:0_16:1) 30.3731 M-H 807.5029 PI(18:0_18:1) 34.8275 M-H 863.5655 PI(18:0_20:3) 34.5639 M-H 887.5655 PI(18:0_22:4) 34.7203 M-H 913.5812 PI(18:0_22:5) 33.3241 M-H 911.5655 PS(16:0_16:1) 30.7472 M-H 732.4821 PS(18:0_22:5) 33.8227 M-H 836.5447 PS(18:0_22:6) 33.2294 M-H 834.5291 PS(18:1_18:1) 33.3081 M-H 786.5291 PS(18:1_20:1) 35.3158 M-H 814.5604 METABOLITES_END #END