Summary of project PR001715
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
| 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 |
Summary of all studies in project PR001715
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002754 | Metabolomics analysis of maternal obesity model | Mus musculus | University of Bonn | MS | 2023-08-01 | 1 | 42 | Not available |
| ST002781 | Lipidomics analysis of maternal obesity model - wild type | Mus musculus | University of Bonn | MS | 2023-08-01 | 1 | 28 | Not available |
| ST002782 | Lipidomics analysis of maternal obesity model - knock out | Mus musculus | University of Bonn | MS | 2023-08-01 | 1 | 43 | Not available |
