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 |
