Summary of Study ST002754

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001715. The data can be accessed directly via it's Project DOI: 10.21228/M81D9R This work is supported by NIH grant, U2C- DK119886.

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Study IDST002754
Study TitleMetabolomics analysis of maternal obesity model
Study Summary100μl serum of 11-12 weeks old male mice with a background from various diet groups were processed in Metabolon (https://www.metabolon.com) for metabolics analysis.Diet groups are CDm CDl CD, CDm CDl HFD, CDmHFDl HFD, HFDm CDl CD, HFDm CDl HFD, HFDm HFDl CD and HFDm CDl CD. (m: maternal diet, l: lactation)
Institute
University of Bonn
DepartmentLIMES
LaboratoryMass Lab
Last NameMass
First NameElvira
AddressLIMES-Institute, Carl-Troll-Str. 31, 53115 Bonn, Germany
Emailelvira.mass@uni-bonn.de
Phone+49 02 28 / 73 6 28 48
Submit Date2023-06-14
Num Groups6
Total Subjects42
Num Males42
Analysis Type DetailLC-MS
Release Date2023-08-01
Release Version1
Elvira Mass Elvira Mass
https://dx.doi.org/10.21228/M81D9R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001715
Project DOI:doi: 10.21228/M81D9R
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
Funding Source:DFG
Publications:in preparation
Contributors:Nora Balzer, Iva Splichalova, Hao Huang, Stephan Grein, Lea Seep

Subject:

Subject ID:SU002861
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

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id MOTHER_DIET OFFSPRING_DIET
SA289497UHBO-00931CD_CD CD
SA289498UHBO-00932CD_CD CD
SA289499UHBO-00909CD_CD CD
SA289500UHBO-00930CD_CD CD
SA289501UHBO-00910CD_CD CD
SA289502UHBO-00912CD_CD CD
SA289503UHBO-00911CD_CD CD
SA289504UHBO-00933CD_CD HFD
SA289505UHBO-00914CD_CD HFD
SA289506UHBO-00935CD_CD HFD
SA289507UHBO-00936CD_CD HFD
SA289508UHBO-00915CD_CD HFD
SA289509UHBO-00913CD_CD HFD
SA289510UHBO-00934CD_CD HFD
SA289511UHBO-00919HFD_CD CD
SA289512UHBO-00917HFD_CD CD
SA289513UHBO-00938HFD_CD CD
SA289514UHBO-00939HFD_CD CD
SA289515UHBO-00918HFD_CD CD
SA289516UHBO-00916HFD_CD CD
SA289517UHBO-00937HFD_CD CD
SA289518UHBO-00940HFD_CD HFD
SA289519UHBO-00942HFD_CD HFD
SA289520UHBO-00943HFD_CD HFD
SA289521UHBO-00920HFD_CD HFD
SA289522UHBO-00941HFD_CD HFD
SA289523UHBO-00921HFD_CD HFD
SA289524UHBO-00922HFD_CD HFD
SA289525UHBO-00945HFD_HFD CD
SA289526UHBO-00946HFD_HFD CD
SA289527UHBO-00925HFD_HFD CD
SA289528UHBO-00924HFD_HFD CD
SA289529UHBO-00944HFD_HFD CD
SA289530UHBO-00926HFD_HFD CD
SA289531UHBO-00923HFD_HFD CD
SA289532UHBO-00949HFD_HFD HFD
SA289533UHBO-00950HFD_HFD HFD
SA289534UHBO-00948HFD_HFD HFD
SA289535UHBO-00947HFD_HFD HFD
SA289536UHBO-00927HFD_HFD HFD
SA289537UHBO-00929HFD_HFD HFD
SA289538UHBO-00928HFD_HFD HFD
Showing results 1 to 42 of 42

Collection:

Collection ID:CO002854
Collection Summary:Blood was withdrawn from the mouse and proceeded for serum extraction. The sera were stored at -80°C until shipped to Metabolon. Further preparation was done there.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR002870
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.

Sample Preparation:

Sampleprep ID:SP002867
Sampleprep Summary:Sera were taken and sent to Metabolon. Further sample preparation was done on Metabolon Site. In short, samples were prepared using the automated MicroLab STAR® system from Hamilton Company. Several recovery standards were added prior to the first step in the extraction process for QC purposes. To remove protein, dissociate small molecules bound to protein or trapped in the precipitated protein matrix, and to recover chemically diverse metabolites, proteins were precipitated with methanol under vigorous shaking for 2 min (Glen Mills GenoGrinder 2000) followed by centrifugation. The resulting extract was divided into five fractions: two for analysis by two separate reverse phase (RP)/UPLC-MS/MS methods with positive ion mode electrospray ionization (ESI), one for analysis by RP/UPLC-MS/MS with negative ion mode ESI, one for analysis by HILIC/UPLC-MS/MS with negative ion mode ESI, and one sample was reserved for backup. Samples were placed briefly on a TurboVap® (Zymark) to remove the organic solvent. The sample extracts were stored overnight under nitrogen before preparation for analysis.

Combined analysis:

Analysis ID AN004468 AN004469 AN004470 AN004471
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase HILIC
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um) Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units Peak Area Peak Area Peak Area Peak Area

Chromatography:

Chromatography ID:CH003353
Chromatography Summary:Low pH polar
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003354
Chromatography Summary:Low pH Lipophilic
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003355
Chromatography Summary:High pH
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003356
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:HILIC

MS:

MS ID:MS004215
Analysis ID:AN004468
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proprietary analytical software for integration and peak picking
Ion Mode:POSITIVE
  
MS ID:MS004216
Analysis ID:AN004469
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proprietary analytical software for integration and peak picking
Ion Mode:POSITIVE
  
MS ID:MS004217
Analysis ID:AN004470
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proprietary analytical software for integration and peak picking
Ion Mode:NEGATIVE
  
MS ID:MS004218
Analysis ID:AN004471
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Proprietary analytical software for integration and peak picking
Ion Mode:NEGATIVE
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