Summary of Study ST002782
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST002782 |
| Study Title | Lipidomics analysis of maternal obesity model - knock out |
| 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 Hif1a flox/flox or Hif1a flox/flox;LysMCre/+ mice with a C57BL/6JRcc background, diet groups contain CDm CD, CDm HFD, HFDm CD and HFDm HFD. m: maternal diet |
| Institute | University of Bonn |
| Department | LIMES |
| Laboratory | Mass Lab |
| Last Name | Mass |
| First Name | Elvira |
| Address | Carl-Troll-Str. 31, 53115 Bonn, Germany |
| elvira.mass@uni-bonn.de | |
| Phone | +49 0228 / 73 6 28 48 |
| Submit Date | 2023-07-03 |
| Num Groups | 8 |
| Total Subjects | 43 |
| Analysis Type Detail | MS(Dir. Inf.) |
| Release Date | 2023-08-01 |
| Release Version | 1 |
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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: | SU002889 |
| 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 | diet | genotype |
|---|---|---|---|
| SA298624 | CDCDCD_ko_23 | CD_CD_CD | ko |
| SA298625 | CDCDCD_ko_32 | CD_CD_CD | ko |
| SA298626 | CDCDCD_ko_25 | CD_CD_CD | ko |
| SA298627 | CDCDCD_ko_33 | CD_CD_CD | ko |
| SA298628 | CDCDCD_ko_34 | CD_CD_CD | ko |
| SA298629 | CDCDCD_wt_19 | CD_CD_CD | wt |
| SA298630 | CDCDCD_wt_18 | CD_CD_CD | wt |
| SA298631 | CDCDCD_wt_20 | CD_CD_CD | wt |
| SA298632 | CDCDCD_wt_21 | CD_CD_CD | wt |
| SA298633 | CDCDCD_wt_14 | CD_CD_CD | wt |
| SA298634 | CDCDCD_wt_24 | CD_CD_CD | wt |
| SA298635 | CDCDCD_wt_22 | CD_CD_CD | wt |
| SA298636 | CDCDHFD_ko_35 | CD_CD_HFD | ko |
| SA298637 | CDCDHFD_ko_13 | CD_CD_HFD | ko |
| SA298638 | CDCDHFD_ko_28 | CD_CD_HFD | ko |
| SA298639 | CDCDHFD_ko_12 | CD_CD_HFD | ko |
| SA298640 | CDCDHFD_ko_36 | CD_CD_HFD | ko |
| SA298641 | CDCDHFD_wt_38 | CD_CD_HFD | wt |
| SA298642 | CDCDHFD_wt_37 | CD_CD_HFD | wt |
| SA298643 | CDCDHFD_wt_26 | CD_CD_HFD | wt |
| SA298644 | CDCDHFD_wt_29 | CD_CD_HFD | wt |
| SA298645 | CDCDHFD_wt_11 | CD_CD_HFD | wt |
| SA298646 | HFDCDCD_ko_39 | HFD_CD_CD | ko |
| SA298647 | HFDCDCD_ko_31 | HFD_CD_CD | ko |
| SA298648 | HFDCDCD_ko_27 | HFD_CD_CD | ko |
| SA298649 | HFDCDCD_ko_40 | HFD_CD_CD | ko |
| SA298650 | HFDCDCD_ko_6 | HFD_CD_CD | ko |
| SA298651 | HFDCDCD_wt_16 | HFD_CD_CD | wt |
| SA298652 | HFDCDCD_wt_15 | HFD_CD_CD | wt |
| SA298653 | HFDCDCD_wt_5 | HFD_CD_CD | wt |
| SA298654 | HFDCDCD_wt_42 | HFD_CD_CD | wt |
| SA298655 | HFDCDCD_wt_41 | HFD_CD_CD | wt |
| SA298656 | HFDHFDHFD_ko_2 | HFD_HFD_HFD | ko |
| SA298657 | HFDHFDHFD_ko_17 | HFD_HFD_HFD | ko |
| SA298658 | HFDHFDHFD_ko_4 | HFD_HFD_HFD | ko |
| SA298659 | HFDHFDHFD_ko_7 | HFD_HFD_HFD | ko |
| SA298660 | HFDHFDHFD_ko_3 | HFD_HFD_HFD | ko |
| SA298661 | HFDHFDHFD_ko_10 | HFD_HFD_HFD | ko |
| SA298662 | HFDHFDHFD_ko_30 | HFD_HFD_HFD | ko |
| SA298663 | HFDHFDHFD_wt_8 | HFD_HFD_HFD | wt |
| SA298664 | HFDHFDHFD_wt_43 | HFD_HFD_HFD | wt |
| SA298665 | HFDHFDHFD_wt_1 | HFD_HFD_HFD | wt |
| SA298666 | HFDHFDHFD_wt_9 | HFD_HFD_HFD | wt |
| Showing results 1 to 43 of 43 |
Collection:
| Collection ID: | CO002882 |
| 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. |
| Sample Type: | Liver |
Treatment:
| Treatment ID: | TR002898 |
| 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: | SP002895 |
| 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 |
Combined analysis:
| Analysis ID | AN004529 |
|---|---|
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | none |
| Column | none |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Exactive Plus Orbitrap |
| Ion Mode | POSITIVE |
| Units | pmol/mg |
Chromatography:
| Chromatography ID: | CH003402 |
| Instrument Name: | none |
| Column Name: | none |
| Column Temperature: | none |
| Flow Gradient: | - |
| Flow Rate: | 10 µl/min |
| Injection Temperature: | 260 |
| Solvent A: | 8/5/1 isopropanol/methanol/water; 10 mM ammonium acetate |
| Solvent B: | - |
| Chromatography Type: | None (Direct infusion) |
MS:
| MS ID: | MS004276 |
| Analysis ID: | AN004529 |
| Instrument Name: | Thermo Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | 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. |
| Ion Mode: | POSITIVE |
| Analysis Protocol File: | Lipidomics_Notes.pdf |
