Image data related to the publication "Kupffer cell programming by maternal obesity triggers fatty liver disease"

Citation Metadata

Title title

Image data related to the publication "Kupffer cell programming by maternal obesity triggers fatty liver disease"

Author author

1. Author Name

   Huang, Hao

   Author Affiliation

   University of Bonn

   Author Identifier Scheme

   ORCID

   Author Identifier

   Type Name

   authorIdentifier

   Multiple

   False

   Type Class

   primitive

   Value

   https://orcid.org/0000-0003-3878-3947

   Expandedvalue

   Person Name

   Huang, Hao

   @id

   https://orcid.org/0000-0003-3878-3947

   Scheme

   ORCID

   @type

   https://schema.org/Person

2. Author Name

   Mass, Elvira

   Author Affiliation

   University of Bonn

   Author Identifier Scheme

   ORCID

   Author Identifier

   Type Name

   authorIdentifier

   Multiple

   False

   Type Class

   primitive

   Value

   https://orcid.org/0000-0003-2318-2356

   Expandedvalue

   Person Name

   Mass, Elvira

   @id

   https://orcid.org/0000-0003-2318-2356

   Scheme

   ORCID

   @type

   https://schema.org/Person

Dataset Contact datasetContact

1. Dataset Contact Name

   Mass, Elvira

   Dataset Contact Affiliation

   University of Bonn

   Dataset Contact Email

   elvira.mass@uni-bonn.de

Ds Description dsDescription

1. Ds Description Value

   Kupffer cells (KCs) are tissue-resident macrophages which colonize the liver early during embryogenesis. Upon liver colonization, KCs rapidly acquire a tissue-specific transcriptional signature, mature alongside the developing liver, and adapt to its functions. Throughout development and adulthood, KCs perform distinct core functions essential for liver and organismal homeostasis, including supporting fetal erythropoiesis, postnatal erythrocyte recycling, and liver metabolism. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs promote lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonates born to obese mothers, followed by replenishment with naïve monocytes, rescues fatty liver disease. Further, genetic ablation of hypoxia-inducible factor alpha (Hif1a) in macrophages during gestation prevents the metabolic programming of KCs from oxidative phosphorylation to glycolysis, thereby averting the development of fatty liver disease. These results establish developmental perturbation of KC functions as a causal factor in fatty liver disease in adulthood and position fetal-derived macrophages as critical intergenerational messengers within the concept of developmental origins of health and diseases.

Subject subject

1. Medicine, Health and Life Sciences

Subject Refinement subjectRefinement

1. Subject Refinement Value

   Immunology

Free Keyword freeKeyword

1. Free Keyword Value

   Kupffer cells

2. Free Keyword Value

   fatty liver

3. Free Keyword Value

   maternal obesity

Publication publication

1. Publication Relation Type

   IsSupplementTo

   Publication Citation

   Huang, H., Balzer, N.R., Seep, L. et al. Kupffer cell programming by maternal obesity triggers fatty liver disease. Nature 644, 790–798 (2025).

   Publication IDType

   doi

   Publication IDNumber

   10.1038/s41586-025-09190-w

   Publication URL

   https://doi.org/10.1038/s41586-025-09190-w

Notes Text notesText

File Description: “Maternal_Obesity_Oil-red-O_WT_cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. Mice were of C57BL/6 Jrcc WT background.There are in total 6 diet groups indicated with CD meaning control diet, HFD standing for high fat diet. The first diet is the diet of the bearing dam, the second is the diet of the foster mother, and the third is the diet the mice received after weaning. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication. “Maternal_Obesity_Oil-red-O_Hif1a_cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. There are in total 4 diet groups indicated with CD meaning control diet, HFD standing for high fat diet. The first diet is the diet of the bearing dam and foster mother, and the second is the diet the mice received after weaning. There are 2 genotypes, WT is Hif1a-f/f; LysM-Cre/+ and KO is Hif1a-f/f; LysM-+/+ litter mate. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication. “Maternal_Obesity_Oil-red-O_Clec4f-DTR_cohort.zip” contains all Oil-red-O (ORO) staining pictures taken with a 40X object. All mice were born to HFD-fed dam, fostered by CD-fed mother, and received CD after weaning. There are 2 genotypes, Clec4f-+/+ and Clec4f-DTR/+. All mice received diphtheria toxin at postnatal day (P) 0, which induces apoptosis of Kupffer cells, and Clec4f-+/+ mice and a group Clec4f-DTR/+ mice recieved monocyte/hematopoietic stem and progenitor cell transfer at P1 (indicated as DT + cells). The group of Clec4f-DTR/+ mice receiving DT only is marked with “DT only”. All pictures were used to quantify the lipid content of the liver, shown as “ORO Area (%)” in the figure of the linked publication. "Hif1a_P0_liver_macs_HFD_or_CD-fed_dams.zip“ contains immunofluorescence staining pictures of P0 liver macrophages (stained by F4/80) and the Hif1a staining signal within the liver macrophages. Individual pictures are individual cells used to quantify the ratio of Hif1a signal between nuclei and cytoplasm. Cells are either from P0 mice born to HFD-fed or CD-fed dams as indicated on the files. "Hepatocyte_lipid_accumulation_with_factors.zip" contain images of hepatocytes and their LD540 signal 2 hours after the addition of TNFa, ApoE or ApoA1. Bright field imaged were used to quantify the amount of hepatocytes. LD540 images were used to quantify the LD540 intensity, i.e. lipid content in hepatocytes. Excel file in the compressed file shows the layout of the 24-well cell culture plate for the experiment. "Hepatocyte_lipid_accumulation_cultured_with_KCs.zip“ contain images of hepatocytes and their LD540 signal at base-line (0h) or 3 or 4 hours after the addition of Kupffer cells isolated from CDCDCD or HFDCDCD mice. Bright field imaged were used to quantify the amount of hepatocytes. LD540 images were used to quantify the LD540 intensity, i.e. lipid content in hepatocytes. Excel file in the compressed file shows the layout of the 24-well cell culture plate for the experiment.

Language language

1. English

Grant Number grantNumber

1. Grant Number Agency

   DFG, German Research Foundation

   Grant Number Value

   Germany’s Excellence Strategy-EXC2151-390873048, SFB1454

Depositor depositor

Huang, Hao

Date Of Deposit dateOfDeposit

2025-02-12

Related Datasets relatedDatasets

1. All the trancriptomics and multi-omics data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237408.
2. Metabolome data is available at Metabolomics Workbench where it has been assigned with the Study ID ST002754 within the same project as the Lipidome data (DOI: http://dx.doi.org/10.21228/M81D9R).
3. Detailed information about every package used, including all dependencies, along with their respective versions, can be found in the renv.lock file located in the GitHub repository (https://github.com/LeaSeep/MaternalObesity) generated with the renv package. A snapshot of the GitHub repository can be found on Zenodo (https://doi.org/10.5281/zenodo.14287647).