#METABOLOMICS WORKBENCH jgengatharan_20240725_092925 DATATRACK_ID:5033 STUDY_ID:ST003351 ANALYSIS_ID:AN005492 PROJECT_ID:PR002085 VERSION 1 CREATED_ON July 26, 2024, 8:09 am #PROJECT PR:PROJECT_TITLE Altered sphingolipid biosynthetic flux and lipoprotein trafficking contribute to PR:PROJECT_TITLE trans fat-induced atherosclerosis PR:PROJECT_SUMMARY The goal of the project is to determine the role of sphingolipid metabolism in PR:PROJECT_SUMMARY atherosclerosis induced by dietary trans fat. We analyzed lipid metabolites in PR:PROJECT_SUMMARY Huh7 cells following various fatty acid treatments, with specific focus on cis PR:PROJECT_SUMMARY and trans unsaturated fatty acids. Additionally, we analyzed lipid metabolites PR:PROJECT_SUMMARY in plasma and liver of Ldlr-/- mice fed high-fat diets enriched in cis or trans PR:PROJECT_SUMMARY fatty acids in the presence or absence of myriocin, a pharmacological inhibitor PR:PROJECT_SUMMARY of SPT, the initial rate-limiting enzyme of sphingolipid biosynthesis. PR:INSTITUTE Salk Institute for Biological Studies PR:LAST_NAME Gengatharan PR:FIRST_NAME Jivani PR:ADDRESS 10010 N Torrey Pines Rd, La Jolla, CA, 92037, USA PR:EMAIL jivani14@gmail.com PR:PHONE (858) 453-4100 #STUDY ST:STUDY_TITLE Incorporation of various fatty acids in long-chain base of sphingolipids in Huh7 ST:STUDY_TITLE cells ST:STUDY_SUMMARY We analyzed hydrolyzed long-chain bases (LCBs) in Huh7 cells treated with ST:STUDY_SUMMARY various BSA-conjugated fatty acids. ST:INSTITUTE Salk Institute for Biological Studies ST:LAST_NAME Gengatharan ST:FIRST_NAME Jivani ST:ADDRESS 10010 N Torrey Pines Rd, La Jolla, CA, 92037, USA ST:EMAIL jivani14@gmail.com ST:PHONE (858) 453-4100 #SUBJECT SU:SUBJECT_TYPE Cultured cells SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:CELL_STRAIN_DETAILS Huh7 #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 - Huh7_palm_C16_1 Sample source:Huh7 cells | Treatment:BSA-palmitate RAW_FILE_NAME(Raw file name)=Huh7_palm_C16_1.d SUBJECT_SAMPLE_FACTORS - Huh7_palm_C16_2 Sample source:Huh7 cells | Treatment:BSA-palmitate RAW_FILE_NAME(Raw file name)=Huh7_palm_C16_2.d SUBJECT_SAMPLE_FACTORS - Huh7_palm_C16_3 Sample source:Huh7 cells | Treatment:BSA-palmitate RAW_FILE_NAME(Raw file name)=Huh7_palm_C16_3.d SUBJECT_SAMPLE_FACTORS - Huh7_C17_1 Sample source:Huh7 cells | Treatment:BSA-heptadecanoate RAW_FILE_NAME(Raw file name)=Huh7_C17_1.d SUBJECT_SAMPLE_FACTORS - Huh7_C17_2 Sample source:Huh7 cells | Treatment:BSA-heptadecanoate RAW_FILE_NAME(Raw file name)=Huh7_C17_2.d SUBJECT_SAMPLE_FACTORS - Huh7_C17_3 Sample source:Huh7 cells | Treatment:BSA-heptadecanoate RAW_FILE_NAME(Raw file name)=Huh7_C17_3.d SUBJECT_SAMPLE_FACTORS - Huh7_stearic_C18_1 Sample source:Huh7 cells | Treatment:BSA-stearate RAW_FILE_NAME(Raw file name)=Huh7_stearic_C18_1.d SUBJECT_SAMPLE_FACTORS - Huh7_stearic_C18_2 Sample source:Huh7 cells | Treatment:BSA-stearate RAW_FILE_NAME(Raw file name)=Huh7_stearic_C18_2.d SUBJECT_SAMPLE_FACTORS - Huh7_stearic_C18_3 Sample source:Huh7 cells | Treatment:BSA-stearate RAW_FILE_NAME(Raw file name)=Huh7_stearic_C18_3.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC16_1 Sample source:Huh7 cells | Treatment:BSA-isoC16 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC16_1.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC16_2 Sample source:Huh7 cells | Treatment:BSA-isoC16 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC16_2.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC16_3 Sample source:Huh7 cells | Treatment:BSA-isoC16 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC16_3.d SUBJECT_SAMPLE_FACTORS - Huh7_anteisoC17_1 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_anteisoC17_1.d SUBJECT_SAMPLE_FACTORS - Huh7_anteisoC17_2 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_anteisoC17_2.d SUBJECT_SAMPLE_FACTORS - Huh7_anteisoC17_3 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_anteisoC17_3.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC17_1 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC17_1.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC17_2 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC17_2.d SUBJECT_SAMPLE_FACTORS - Huh7_isoC17_3 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 RAW_FILE_NAME(Raw file name)=Huh7_isoC17_3.d SUBJECT_SAMPLE_FACTORS - Huh7_oleic_C18-1cis_1 Sample source:Huh7 cells | Treatment:BSA-oleate RAW_FILE_NAME(Raw file name)=Huh7_oleic_C18-1cis_1.d SUBJECT_SAMPLE_FACTORS - Huh7_oleic_C18-1cis_2 Sample source:Huh7 cells | Treatment:BSA-oleate RAW_FILE_NAME(Raw file name)=Huh7_oleic_C18-1cis_2.d SUBJECT_SAMPLE_FACTORS - Huh7_oleic_C18-1cis_3 Sample source:Huh7 cells | Treatment:BSA-oleate RAW_FILE_NAME(Raw file name)=Huh7_oleic_C18-1cis_3.d SUBJECT_SAMPLE_FACTORS - Huh7_elaidic_C18-1trans_1 Sample source:Huh7 cells | Treatment:BSA-elaidate RAW_FILE_NAME(Raw file name)=Huh7_elaidic_C18-1trans_1.d SUBJECT_SAMPLE_FACTORS - Huh7_elaidic_C18-1trans_2 Sample source:Huh7 cells | Treatment:BSA-elaidate RAW_FILE_NAME(Raw file name)=Huh7_elaidic_C18-1trans_2.d SUBJECT_SAMPLE_FACTORS - Huh7_elaidic_C18-1trans_3 Sample source:Huh7 cells | Treatment:BSA-elaidate RAW_FILE_NAME(Raw file name)=Huh7_elaidic_C18-1trans_3.d #COLLECTION CO:COLLECTION_SUMMARY Cells (~400,000) were spiked with internal standards sphinganine-d7 (Avanti CO:COLLECTION_SUMMARY Polar Lipids, Cat# 860658) and sphingosine-d7 (Avanti Polar Lipids, Cat# 860657) CO:COLLECTION_SUMMARY and were scraped with 0.5 mL methanol. CO:SAMPLE_TYPE Cultured cells #TREATMENT TR:TREATMENT_SUMMARY Huh7 cells were treated with 100 µM BSA-palmitate, BSA-heptadecanoate, TR:TREATMENT_SUMMARY BSA-stearate, BSA-isoC16:0, BSA-anteisoC17:0, BSA-isoC17:0, BSA-oleate, or TR:TREATMENT_SUMMARY BSA-elaidate for 48 hours. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cells (~400,000) were spiked with internal standards sphinganine-d7 (Avanti SP:SAMPLEPREP_SUMMARY Polar Lipids, Cat# 860658) and sphingosine-d7 (Avanti Polar Lipids, Cat# 860657) SP:SAMPLEPREP_SUMMARY and were scraped with 0.5 mL methanol. Homogenate aliquot of 50 µL was taken to SP:SAMPLEPREP_SUMMARY determine protein content using the BCA protein assay (Thermo Fisher SP:SAMPLEPREP_SUMMARY Scientific). Samples were placed on a mixer for 1 hr at 37°C and then SP:SAMPLEPREP_SUMMARY centrifuged for 5 min at 16,000g. The MeOH was supernatant transferred to a new SP:SAMPLEPREP_SUMMARY Eppendorf tube and hydrolyzed for 16 hr at 65°C. 100 µL 10M KOH, 625 µL SP:SAMPLEPREP_SUMMARY chloroform, 100 µL 2N NH4OH, and 500 µL alkaline water were added to samples SP:SAMPLEPREP_SUMMARY followed by vortexing for 5 min and centrifugation for 5 min at 16,000g. The SP:SAMPLEPREP_SUMMARY lower organic phase was washed 3 times with alkaline water and dried under air. SP:SAMPLEPREP_SUMMARY After dried extracts were resuspended in 60 µl Buffer B, 5 µL of sample was SP:SAMPLEPREP_SUMMARY injected. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1260 Infinity II CH:COLUMN_NAME Thermo Hypersil GOLD C18 Selectivity (100 x 2.1 mm, 1.9 µm) CH:SOLVENT_A 60% methanol 40% water; 0.1% formic acid; 5 mM ammonium formate CH:SOLVENT_B 100% methanol; 0.1% formic acid; 5 mM ammonium formate CH:FLOW_GRADIENT 0 min, 40%B; 0.5 min, 40%B; 16 min, 100%B; 25.5 min, 100%B; 26 min, 40%B CH:FLOW_RATE 0.2 ml/min CH:COLUMN_TEMPERATURE 40 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Agilent 6460 QQQ MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS Agilent Masshunter #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples Huh7_palm_C16_1 Huh7_palm_C16_2 Huh7_palm_C16_3 Huh7_C17_1 Huh7_C17_2 Huh7_C17_3 Huh7_stearic_C18_1 Huh7_stearic_C18_2 Huh7_stearic_C18_3 Huh7_isoC16_1 Huh7_isoC16_2 Huh7_isoC16_3 Huh7_anteisoC17_1 Huh7_anteisoC17_2 Huh7_anteisoC17_3 Huh7_isoC17_1 Huh7_isoC17_2 Huh7_isoC17_3 Huh7_oleic_C18-1cis_1 Huh7_oleic_C18-1cis_2 Huh7_oleic_C18-1cis_3 Huh7_elaidic_C18-1trans_1 Huh7_elaidic_C18-1trans_2 Huh7_elaidic_C18-1trans_3 Factors Sample source:Huh7 cells | Treatment:BSA-palmitate Sample source:Huh7 cells | Treatment:BSA-palmitate Sample source:Huh7 cells | Treatment:BSA-palmitate Sample source:Huh7 cells | Treatment:BSA-heptadecanoate Sample source:Huh7 cells | Treatment:BSA-heptadecanoate Sample source:Huh7 cells | Treatment:BSA-heptadecanoate Sample source:Huh7 cells | Treatment:BSA-stearate Sample source:Huh7 cells | Treatment:BSA-stearate Sample source:Huh7 cells | Treatment:BSA-stearate Sample source:Huh7 cells | Treatment:BSA-isoC16 0 Sample source:Huh7 cells | Treatment:BSA-isoC16 0 Sample source:Huh7 cells | Treatment:BSA-isoC16 0 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 Sample source:Huh7 cells | Treatment:BSA-anteisoC17 0 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 Sample source:Huh7 cells | Treatment:BSA-isoC17 0 Sample source:Huh7 cells | Treatment:BSA-oleate Sample source:Huh7 cells | Treatment:BSA-oleate Sample source:Huh7 cells | Treatment:BSA-oleate Sample source:Huh7 cells | Treatment:BSA-elaidate Sample source:Huh7 cells | Treatment:BSA-elaidate Sample source:Huh7 cells | Treatment:BSA-elaidate SA d18:0 d7 487439 483485 408086 606749 523735 585393 451950 474459 600506 493873 652397 360955 528593 506249 416904 606694 534524 456108 385456 398656 473405 453593 571694 650199 SA d18:0 iso 1065514 1230201 666064 SA d18:0 3523535 3286078 2799824 1775676 1669315 1787317 3578812 3120892 3589312 756486 957293 548615 560743 612266 487470 1197030 1257891 1043636 2315259 2648159 2547963 2597841 2625934 2667793 SA d19:0 anteiso 1708411 1748192 1339358 SA d19:0 iso 1490964 1488599 1279156 SA d19:0 28274 23586 18530 1478048 1310276 1465699 47698 39507 47085 8010 11885 5454 13880 22318 12088 30000 25930 7117 32289 39525 38421 33493 35766 35030 SA d20:0 124933 94718 78199 62755 58033 63841 942317 880434 1111782 24046 38042 17213 55886 41846 26581 46877 46009 33864 77010 95832 91237 103679 98717 123375 SA d20:1, 11E 888199 927596 1125764 SA d20:1, 11Z 59756 44607 32404 10870 7423 28748 74089 58838 80643 3658 20881 1068 4721 8925 1095 16160 15503 7671 78330 89988 101757 20737 19165 26142 SO d18:1 d7 1641278 1549776 1441947 2024907 1751598 1937900 1491577 1654773 1990372 1664939 1943109 1268755 2255849 2194090 1857100 2020858 1876073 1629124 1293428 1421897 1632613 1564296 1850749 2167655 SO d18:1 iso 20693034 24461667 13301466 SO d18:1 49892673 47881829 39846649 31825721 29392406 30805227 44663681 41093452 47952432 22498262 27076184 15341605 27468942 30130068 23587502 28925393 28287398 25299199 33736081 40059893 38055077 35918661 38734855 36756231 SO d19:1 anteiso 28285330 30759883 24979617 SO d19:1 iso 24343000 26747539 20695922 SO d19:1 625766 586907 421489 14850698 12427972 14661117 815954 831394 1011972 205299 262362 138684 258606 172066 228012 1089401 1161857 1074167 739133 939274 1057521 587259 677812 712694 SO d20:1 2628669 2494825 1876957 1570355 1379482 1584732 13441556 13643549 16524544 651693 921697 435146 994609 962089 684656 1133835 1109721 913708 2798711 3381871 3218098 1944530 2142445 2270642 SO d20:2, 11E 5918863 6525083 7069204 SO d20:2, 11Z 188638 179524 91713 101791 93886 90662 384485 317670 386901 75945 125124 50123 53688 50268 45939 84759 84563 72360 291574 378328 332388 136788 119109 115635 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Precursor Ion Product Ion SA d18:0 d7 309.4 291.5 SA d18:0 iso 302.4 284.4 SA d18:0 302.4 284.4 SA d19:0 anteiso 316.4 298.4 SA d19:0 iso 316.4 298.4 SA d19:0 316.4 298.4 SA d20:0 330.3 312.4 SA d20:1, 11E 328.4 310.4 SA d20:1, 11Z 328.4 310.4 SO d18:1 d7 307.3 289.4 SO d18:1 iso 300.4 282.4 SO d18:1 300.4 282.4 SO d19:1 anteiso 314.4 296.4 SO d19:1 iso 314.4 296.4 SO d19:1 314.4 296.4 SO d20:1 328.4 310.4 SO d20:2, 11E 326.4 308.4 SO d20:2, 11Z 326.4 308.4 METABOLITES_END #END