Summary of Study ST003702
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 PR002234. The data can be accessed directly via it's Project DOI: 10.21228/M8VJ9K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003702 |
| Study Title | Kupffer cells control neonatal hepatic glucose metabolism via Igf1 signaling - lipidomics analysis of postnatal day 0 murine livers after macrophages depletion using Csf1r conditional KO |
| Study Type | lipidomics analysis of P0 livers from mice after macrophages depletion by Csf1r conditional KO |
| Study Summary | During perinatal development, liver metabolism is tightly regulated to ensure energy supply for the newborn. Before birth, glycogen is stored in hepatocytes and later metabolized to glucose, meeting the energy demands of the neonate. Shortly after birth, lipogenesis begins, driven by the transcriptional activation of enzymes involved in fatty acid oxidation. These processes are thought to be largely regulated by systemic insulin and glucagon levels. However, the role of liver-derived local factors in neonatal hepatocyte metabolism remains unexplored. Kupffer cells (KCs), the liver’s resident macrophages, colonize the fetal liver early in embryogenesis and support liver metabolism in adulthood. Yet, whether KCs influence neonatal hepatocyte metabolism is unknown. Here, using conditional knockout mouse models targeting macrophages (Csf1r-flox Tnfrsf11a-Cre), we demonstrate that yolk sac-derived KCs play a critical role in hepatocyte glycogen storage and function by regulating the TCA cycle - a role that monocyte-derived KC-like cells cannot substitute. in order to check the lipid levels after birth, Newborn pups were collected and the different lipid species were assessd by lipidomics analysis using mass spectrometer. |
| Institute | University of Bonn |
| Department | Developmental Biology of the Immune System, The Life & Medical Sciences Institute (LIMES) |
| Laboratory | Mass Lab |
| Last Name | Makdissi |
| First Name | Nikola |
| Address | Carl Troll straße 31 |
| nmakdissi@uni-bonn.de | |
| Phone | 02 28 / 73 - 6 2794 |
| Submit Date | 2025-01-15 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-02-11 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002234 |
| Project DOI: | doi: 10.21228/M8VJ9K |
| Project Title: | Kupffer cells control neonatal hepatic glucose metabolism via Igf1 signaling |
| Project Type: | lipidomics analysis |
| Project Summary: | During perinatal development, liver metabolism is tightly regulated to ensure energy supply for the newborn. Before birth, glycogen is stored in hepatocytes and later metabolized to glucose, meeting the energy demands of the neonate. Shortly after birth, lipogenesis begins, driven by the transcriptional activation of enzymes involved in fatty acid oxidation. These processes are thought to be largely regulated by systemic insulin and glucagon levels. However, the role of liver-derived local factors in neonatal hepatocyte metabolism remains unexplored. Kupffer cells (KCs), the liver’s resident macrophages, colonize the fetal liver early in embryogenesis and support liver metabolism in adulthood. Yet, whether KCs influence neonatal hepatocyte metabolism is unknown. Here, using conditional knockout mouse models targeting macrophages, we demonstrate that yolk sac-derived KCs play a critical role in hepatocyte glycogen storage and function by regulating the TCA cycle - a role that monocyte-derived KC-like cells cannot substitute. Newborn pups lacking KCs mobilize glycogen more rapidly, a process regulated by insulin-like growth factor 1 (Igf1) production. Our findings reveal that macrophages are a major source of Igf1 at birth and that local Igf1 production by KCs is essential for balanced hepatocyte metabolism. |
| Institute: | University of Bonn |
| Department: | Developmental Biology of the Immune System, The Life & Medical Sciences Institute (LIMES) |
| Laboratory: | Mass Lab |
| Last Name: | Makdissi |
| First Name: | Nikola |
| Address: | Carl Troll straße 31, Bonn |
| Email: | nmakdissi@uni-bonn.de |
| Phone: | 02 28 / 73 - 6 2794 |
Subject:
| Subject ID: | SU003834 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | genotype |
|---|---|---|
| SA405331 | Csf1r KO 1 | KO |
| SA405332 | Csf1r KO 2 | KO |
| SA405333 | Csf1r KO 3 | KO |
| SA405334 | Csf1r KO 4 | KO |
| SA405335 | Csf1r KO 5 | KO |
| SA405336 | Csf1r KO 6 | KO |
| SA405337 | Csf1r WT 1 | WT |
| SA405338 | Csf1r WT 2 | WT |
| SA405339 | Csf1r WT 3 | WT |
| SA405340 | Csf1r WT 4 | WT |
| SA405341 | Csf1r WT 5 | WT |
| SA405342 | Csf1r WT 6 | WT |
| Showing results 1 to 12 of 12 |
Collection:
| Collection ID: | CO003827 |
| Collection Summary: | The Csf1r-flox Tnfrsf11aCre livers of P0 pups were collected in cold PBS then snap frozen in Nitrogen. |
| Sample Type: | Liver |
Treatment:
| Treatment ID: | TR003843 |
| Treatment Summary: | No treatment. P0 livers from the Csfrflox Tnfrsf11aeGFPCre mouse model were snap frozen in Nitrogen. The pups were WT(Csf1rf/f Tnfrsf11aeGFP+/+) and KO (Csf1rf/f Tnfrsf11aeGFPCre/+) |
Sample Preparation:
| Sampleprep ID: | SP003840 |
| Sampleprep Summary: | Lipid extraction and tandem mass spectrometry: To evaluate differences in hepatic lipid metabolism tandem mass spectrometry of extracted lipids was performed. For this purpose, 10 mg liver tissue was homogenized in 500 μL ddH2O on ice. Then, 50 μL of the homogenate was transferred into a fresh Eppendorf tube and 500 μL Extraction Mix (CHCl3/MeOH 1/5 containing the following internal standards: 210 pmol PE(31:1), 396 pmol PC(31:1), 98 pmol PS(31:1), 84 pmol PI(34:0), 56 pmol PA(31:1), 51 pmol PG (28:0), 28 pmol CL(56:0), 39 pmol LPA (17:0), 35 pmol LPC(17:1), 38 pmol LPE (17:0), 32 pmol Cer(17:0), 99 pmol, SM(17:0), 55 pmol GlcCer(12:0), 14 pmol GM3 (18:0-D3), 339 pmol TG(50:1-d4), 111 pmol, CE(17:1), 64 pmol DG(31:1), 103 pmol MG(17:1), 724 pmol Chol(d6) and 45 pmol Car(15:0) was added. After 2 min of sonication in a bath sonicator, the samples were spun at 20,000 g for 2 min. The supernatant was collected in a new Eppendorf tube and 200 μL chloroform and 750 μL of 1 M Ammonium acetate (NH4Ac) in ddH2O were added. Following quick manual shaking, the samples were centrifuged at 20,000 g for 2 min again. The upper phase was carefully removed, and the lower phase was transferred into a new Eppendorf tube. The solvent was evaporated using a SpeedVac Vacuum Concentrator at 45 °C for 20 min. The dried lipids were dissolved in 500 μL Spray Buffer (Isopropanol, Methanol, ddH2O (all MS grade), 10 mM ammonium acetate, 0.1 % acetic acid by sonication for 5 min. Until measurement with a Thermo Q Exactive ™ Plus (Thermo Scientific) using positive mode, the samples were stored at -20 °C. Before the acquisition, the samples were sonicated for 5 min. |
Combined analysis:
| Analysis ID | AN006074 |
|---|---|
| Analysis type | MS |
| Chromatography type | None (Direct infusion) |
| Chromatography system | none |
| Column | none |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | POSITIVE |
| Units | pmol/g liver |
Chromatography:
| Chromatography ID: | CH004613 |
| Instrument Name: | none |
| Column Name: | none |
| Column Temperature: | none |
| Flow Gradient: | none |
| Flow Rate: | none |
| Solvent A: | none |
| Solvent B: | none |
| Chromatography Type: | None (Direct infusion) |
MS:
| MS ID: | MS005781 |
| Analysis ID: | AN006074 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The samples were run on the positive mode and the raw data were processed using LipidXplorer. Analysed data was taken relative to the internal standerd for each species and then the lipid abundance was calculated per gram of tissue. NOTE: "0" values indicate that the metabolite wasn't detected, while the "NA" indicates that the metabolite was detected but wasn't able to be calculated because the internal standard wasn't detected in the individual sample. |
| Ion Mode: | POSITIVE |
