{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002781","ANALYSIS_ID":"AN004528","VERSION":"1","CREATED_ON":"July 14, 2023, 10:43 am"},

"PROJECT":{"PROJECT_TITLE":"Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring","PROJECT_SUMMARY":"Kupffer cells (KCs) are tissue-resident macrophages which colonize the developing liver early during embryogenesis. Throughout development and adulthood, KCs have distinct core functions that are essential for liver and organismal homeostasis, such as supporting fetal erythropoiesis as well as postnatal erythrocyte recycling and liver metabolism. KCs acquire their tissue-specific transcriptional signature immediately after colonizing the liver, mature together with the tissue, and adapt to the tissue’s function. However, whether perturbation of macrophage core functions during development may contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a maternal obesity model to disturb KC functions during gestation. We show that offspring born to obese mothers develop fatty liver disease that is accompanied by a local pro-inflammatory response, a phenotype that is augmented if the offspring is kept on control diet after birth. Further, transcriptional analyses reveal that KCs undergo developmental programming through the maternal high-fat diet, which lasts until adulthood. The offspring’s KC developmental programming is irreversible despite the switch to control diet and leads to increased lipid uptake in hepatocytes mediated via paracrine factors stemming from KCs. The transcriptional programming of KCs and the fatty liver disease phenotype are rescued by genetic depletion of hypoxia-inducible factor alpha (Hif-1alpha) in macrophages during gestation. These results demonstrate that macrophages rely on an undisturbed development to fulfil their core functions and support organ homeostasis during adulthood, and establish developmental programming of KCs as a therapeutic strategy for metabolic disorders, such as fatty liver disease.","INSTITUTE":"University of Bonn","DEPARTMENT":"LIMES","LABORATORY":"Mass Lab","LAST_NAME":"Mass","FIRST_NAME":"Elvira","ADDRESS":"Carl-Troll-Str. 31, 53115 Bonn, Germany","EMAIL":"elvira.mass@uni-bonn.de","PHONE":"+49 0228 / 73 6 28 48","PUBLICATIONS":"in preparation"},

"STUDY":{"STUDY_TITLE":"Lipidomics analysis of maternal obesity model - wild type","STUDY_SUMMARY":"10μl liver tissue of 11-12 weeks old male mice from various diet groups with various genetic background were homogenized and lipids were extracted for shotgun lipidomics experiments. Raw files were converted to .mzml files and imported into and analyzed by LipidXplorer software using custom mfql files to identify sample lipids and internal standards. For further data processing, absolute amounts were calculated using the internal standard intensities followed by the calculated mol% of the identified lipids. For wild-type C57BL/6JRcc mice, diet groups are CDm CDl CD, CDm CDl HFD, CDm HFDl HFD, HFDm CDl CD, HFDm CDl HFD, HFDm HFDl CD and HFDm CDl CD. m: maternal diet, l: lactation phase diet.","INSTITUTE":"University of Bonn","DEPARTMENT":"LIMES","LABORATORY":"Mass Lab","LAST_NAME":"Mass","FIRST_NAME":"Elvira","ADDRESS":"Carl-Troll-Str. 31, 53115 Bonn, Germany","EMAIL":"elvira.mass@uni-bonn.de","PHONE":"+49 0228 / 73 6 28 48","NUM_GROUPS":"6","TOTAL_SUBJECTS":"28"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENOTYPE_STRAIN":"C57BL/6JRcc","AGE_OR_AGE_RANGE":"10-12 weeks","ANIMAL_HOUSING":"specific pathogen-free conditions","ANIMAL_LIGHT_CYCLE":"12-h light/dark cycle"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"103",
"Sample ID":"CD_CD_CD_103",
"Factors":{"diet":"CD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"105",
"Sample ID":"CD_CD_CD_105",
"Factors":{"diet":"CD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"106",
"Sample ID":"CD_CD_CD_106",
"Factors":{"diet":"CD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"200",
"Sample ID":"CD_CD_HFD_200",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"201",
"Sample ID":"CD_CD_HFD_201",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"203",
"Sample ID":"CD_CD_HFD_203",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"205",
"Sample ID":"CD_CD_HFD_205",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"206",
"Sample ID":"CD_CD_HFD_206",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"207",
"Sample ID":"CD_CD_HFD_207",
"Factors":{"diet":"CD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalLean"}
},
{
"Subject ID":"800",
"Sample ID":"HFD_CD_CD_800",
"Factors":{"diet":"HFD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"801",
"Sample ID":"HFD_CD_CD_801",
"Factors":{"diet":"HFD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"802",
"Sample ID":"HFD_CD_CD_802",
"Factors":{"diet":"HFD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"803",
"Sample ID":"HFD_CD_CD_803",
"Factors":{"diet":"HFD_CD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"700",
"Sample ID":"HFD_CD_HFD_700",
"Factors":{"diet":"HFD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"701",
"Sample ID":"HFD_CD_HFD_701",
"Factors":{"diet":"HFD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"702",
"Sample ID":"HFD_CD_HFD_702",
"Factors":{"diet":"HFD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"703",
"Sample ID":"HFD_CD_HFD_703",
"Factors":{"diet":"HFD_CD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"601",
"Sample ID":"HFD_HFD_CD_601",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"602",
"Sample ID":"HFD_HFD_CD_602",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"603",
"Sample ID":"HFD_HFD_CD_603",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"604",
"Sample ID":"HFD_HFD_CD_604",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"605",
"Sample ID":"HFD_HFD_CD_605",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"606",
"Sample ID":"HFD_HFD_CD_606",
"Factors":{"diet":"HFD_HFD_CD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"500",
"Sample ID":"HFD_HFD_HFD_500",
"Factors":{"diet":"HFD_HFD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"501",
"Sample ID":"HFD_HFD_HFD_501",
"Factors":{"diet":"HFD_HFD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"502",
"Sample ID":"HFD_HFD_HFD_502",
"Factors":{"diet":"HFD_HFD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"503",
"Sample ID":"HFD_HFD_HFD_503",
"Factors":{"diet":"HFD_HFD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
},
{
"Subject ID":"504",
"Sample ID":"HFD_HFD_HFD_504",
"Factors":{"diet":"HFD_HFD_HFD"},
"Additional sample data":{"MaternalDiet":"MaternalObese"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Livers were isolated from PBS-perfused mice, and 10 µg was homogenized in ddH2O using a Precellys homogenizer (Peqlab Biotechnology). The mice were subjected different diet schemes.","COLLECTION_PROTOCOL_FILENAME":"Lipidomics_Notes.pdf","SAMPLE_TYPE":"Liver"},

"TREATMENT":{"TREATMENT_SUMMARY":"Samples were taken from the developed Maternal Obesity model. This model was generated as described in the Material and Methods section. No additional treatment was done."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"In this experiment, mouse livers were isolated and processed to extract lipids for analysis. The livers were homogenized and subjected to a series of centrifugation and phase separation steps to obtain the lipid samples. The extracted lipids were then prepared for further analysis by adding specific internal standards and a spray buffer, allowing for subsequent characterization and investigation.","SAMPLEPREP_PROTOCOL_FILENAME":"Lipidomics_Notes.pdf"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"None (Direct infusion)","INSTRUMENT_NAME":"Thermo Q Exactive Plus","COLUMN_NAME":"none","SOLVENT_A":"8/5/1 isopropanol/methanol/water; 10 mM ammonium acetate","SOLVENT_B":"-","FLOW_GRADIENT":"-","FLOW_RATE":"10 µl/min","COLUMN_TEMPERATURE":"none","INJECTION_TEMPERATURE":"260"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS","ANALYSIS_PROTOCOL_FILE":"Lipidomics_Notes.pdf"},

"MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Plus Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"Other","ION_MODE":"POSITIVE","MS_COMMENTS":"Thermo Q Exactive Plus spectrometer equipped with the HESI II ion source. MS1 spectra (resolution 280 000) were recorded in 100 m/z windows from 250 to 1200 m/z (pos.) and 200 - 1700 m/z (neg.) followed by recording MS/MS spectra (res. 70 000) by data-independent acquisition in 1 m/z windows from 200 to 1200 (pos.) and 200 to 1700 (neg.) m/z. Raw files were converted to .mzml files and imported into and analyzed by LipidXplorer software using custom mfql files to identify sample lipids and internal standards. For further data processing, absolute amounts were calculated using the internal standard intensities followed by the calculated mol% of the identified lipids."},

"MS_METABOLITE_DATA":{
"Units":"pmol/mg",

"Data":[{"Metabolite":"Car(14:2)","CD_CD_CD_103":"0","CD_CD_CD_105":"0","CD_CD_CD_106":"0","CD_CD_HFD_200":"0","CD_CD_HFD_201":"0","CD_CD_HFD_203":"0","CD_CD_HFD_205":"0","CD_CD_HFD_206":"0","CD_CD_HFD_207":"0","HFD_CD_CD_800":"0","HFD_CD_CD_801":"0.0398697387552326","HFD_CD_CD_802":"0.0131226379951146","HFD_CD_CD_803":"0","HFD_CD_HFD_700":"0","HFD_CD_HFD_701":"0","HFD_CD_HFD_702":"0","HFD_CD_HFD_703":"0","HFD_HFD_CD_601":"0","HFD_HFD_CD_602":"0","HFD_HFD_CD_603":"0","HFD_HFD_CD_604":"0","HFD_HFD_CD_605":"0","HFD_HFD_CD_606":"0.0226792005224341","HFD_HFD_HFD_500":"0.0126305118250996","HFD_HFD_HFD_501":"0","HFD_HFD_HFD_502":"0.0186284496151037","HFD_HFD_HFD_503":"0","HFD_HFD_HFD_504":"0"},{"Metabolite":"Car(14:1)","CD_CD_CD_103":"0","CD_CD_CD_105":"0","CD_CD_CD_106":"0","CD_CD_HFD_200":"0","CD_CD_HFD_201":"0","CD_CD_HFD_203":"0","CD_CD_HFD_205":"0","CD_CD_HFD_206":"0","CD_CD_HFD_207":"0","HFD_CD_CD_800":"0","HFD_CD_CD_801":"0","HFD_CD_CD_802":"0","HFD_CD_CD_803":"0","HFD_CD_HFD_700":"0","HFD_CD_HFD_701":"0","HFD_CD_HFD_702":"0","HFD_CD_HFD_703":"0","HFD_HFD_CD_601":"0","HFD_HFD_CD_602":"0","HFD_HFD_CD_603":"0","HFD_HFD_CD_604":"0","HFD_HFD_CD_605":"0","HFD_HFD_CD_606":"0.016025621157093","HFD_HFD_HFD_500":"0","HFD_HFD_HFD_501":"0","HFD_HFD_HFD_502":"0","HFD_HFD_HFD_503":"0","HFD_HFD_HFD_504":"0"},{"Metabolite":"Car(14:0)","CD_CD_CD_103":"0.0357961759178418","CD_CD_CD_105":"0.0597883184883349","CD_CD_CD_106":"0.102324249829038","CD_CD_HFD_200":"0.0676382847283264","CD_CD_HFD_201":"0.034613703599907","CD_CD_HFD_203":"0.0412528998680571","CD_CD_HFD_205":"0.0533452986149656","CD_CD_HFD_206":"0.025641872923033","CD_CD_HFD_207":"0.0626041207348066","HFD_CD_CD_800":"0.0423162312526815","HFD_CD_CD_801":"0.0451477174565258","HFD_CD_CD_802":"0.0264493361504403","HFD_CD_CD_803":"0.029037540149126","HFD_CD_HFD_700":"0.0269400887323773","HFD_CD_HFD_701":"0.0346550323487222","HFD_CD_HFD_702":"0.0813820338630483","HFD_CD_HFD_703":"0.0243521118737117","HFD_HFD_CD_601":"0.0508080508015649","HFD_HFD_CD_602":"0.0399224257015423","HFD_HFD_CD_603":"0.0347762045412964","HFD_HFD_CD_604":"0.0261564753391073","HFD_HFD_CD_605":"0.0355794704803317","HFD_HFD_CD_606":"0.0729764584790612","HFD_HFD_HFD_500":"0.0388212027183586","HFD_HFD_HFD_501":"0.0533243674971691","HFD_HFD_HFD_502":"0.044581012911857","HFD_HFD_HFD_503":"0.172271200568986","HFD_HFD_HFD_504":"0.0617971979254339"},{"Metabolite":"Car(16:1)","CD_CD_CD_103":"0.0342156589500069","CD_CD_CD_105":"0.0458468511350729","CD_CD_CD_106":"0.0473635735699607","CD_CD_HFD_200":"0.036503840426306","CD_CD_HFD_201":"0.0505842673211725","CD_CD_HFD_203":"0.0556726735258387","CD_CD_HFD_205":"0.0277713665958891","CD_CD_HFD_206":"0.0334632749227838","CD_CD_HFD_207":"0.05404233552026","HFD_CD_CD_800":"0.0536725501839256","HFD_CD_CD_801":"0.0541735158032887","HFD_CD_CD_802":"0.0289747986460445","HFD_CD_CD_803":"0.0270150330099708","HFD_CD_HFD_700":"0.0261028851729118","HFD_CD_HFD_701":"0.056941984542873","HFD_CD_HFD_702":"0.0438182790055777","HFD_CD_HFD_703":"0.0322261442348875","HFD_HFD_CD_601":"0.047814954381161","HFD_HFD_CD_602":"0","HFD_HFD_CD_603":"0.0387716136421306","HFD_HFD_CD_604":"0.0279686008389476","HFD_HFD_CD_605":"0.038150268718377","HFD_HFD_CD_606":"0.0821869133433691","HFD_HFD_HFD_500":"0.0296501062552331","HFD_HFD_HFD_501":"0.0376993573345873","HFD_HFD_HFD_502":"0.0629679091837805","HFD_HFD_HFD_503":"0.0388998830982624","HFD_HFD_HFD_504":"0.0412760865852195"},{"Metabolite":"Car(16:0)","CD_CD_CD_103":"0.101561699428467","CD_CD_CD_105":"0.134981990788893","CD_CD_CD_106":"0.157014484403502","CD_CD_HFD_200":"0.0963602647788745","CD_CD_HFD_201":"0.189366963268542","CD_CD_HFD_203":"0.259137002752151","CD_CD_HFD_205":"0.177135573683404","CD_CD_HFD_206":"0.173237229697284","CD_CD_HFD_207":"0.249863059560339","HFD_CD_CD_800":"0.224875683580688","HFD_CD_CD_801":"0.175617852894677","HFD_CD_CD_802":"0.0777661061837015","HFD_CD_CD_803":"0.0710009022720645","HFD_CD_HFD_700":"0.121454761539922","HFD_CD_HFD_701":"0.192307023771188","HFD_CD_HFD_702":"0.166505991908359","HFD_CD_HFD_703":"0.144344600738876","HFD_HFD_CD_601":"0.296427471877096","HFD_HFD_CD_602":"0.0819352951246822","HFD_HFD_CD_603":"0.151589050358458","HFD_HFD_CD_604":"0.128743019441765","HFD_HFD_CD_605":"0.169040983899443","HFD_HFD_CD_606":"0.312758151647224","HFD_HFD_HFD_500":"0.173215843777156","HFD_HFD_HFD_501":"0.206655531729044","HFD_HFD_HFD_502":"0.130975991110335","HFD_HFD_HFD_503":"0.208344139811604","HFD_HFD_HFD_504":"0.22936871920082"},{"Metabolite":"Car(18:2)","CD_CD_CD_103":"0.0454231096722863","CD_CD_CD_105":"0.042569300036691","CD_CD_CD_106":"0.0802865506023493","CD_CD_HFD_200":"0.0504254048150637","CD_CD_HFD_201":"0.0669339440820146","CD_CD_HFD_203":"0.0664865015608306","CD_CD_HFD_205":"0.0464418924818285","CD_CD_HFD_206":"0.0657518919037753","CD_CD_HFD_207":"0.0916382303926532","HFD_CD_CD_800":"0.0413115273137975","HFD_CD_CD_801":"0.0501662111431077","HFD_CD_CD_802":"0.0198043001640785","HFD_CD_CD_803":"0","HFD_CD_HFD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