Image data related to the publication "Kupffer cell programming by maternal obesity triggers fatty liver disease"https://doi.org/10.60507/FK2/PP2MPBHuang, HaoMass, Elvirabonndata2025-04-032026-03-24T11:16:37ZKupffer 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.Medicine, Health and Life SciencesEnglishHuang, H., Balzer, N.R., Seep, L. et al. Kupffer cell programming by maternal obesity triggers fatty liver disease. Nature 644, 790–798 (2025)., doi, 10.1038/s41586-025-09190-w, https://doi.org/10.1038/s41586-025-09190-w2025-04-03Huang, Hao2025-02-12All the trancriptomics and multi-omics data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237408.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).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).CC BY 4.0