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@ARTICLE{Huang:280788,
      author       = {Huang, Hao and Balzer, Nora and Seep, Lea and Splichalova,
                      Iva and Blank-Stein, Nelli and Viola, Maria Francesca and
                      Franco Taveras, Eliana and Acil, Kerim and Fink, Diana and
                      Petrovic, Franzisca and Makdissi, Nikola and Bayar, Seyhmus
                      and Mauel, Katharina and Radwaniak, Carolin and Zurkovic,
                      Jelena and Kayvanjoo, Amir H and Wunderling, Klaus and
                      Jessen, Malin and Yaghmour, Mohamed H and Kenner, Lukas and
                      Ulas, Thomas and Grein, Stephan and Schultze, Joachim L and
                      Scott, Charlotte L and Guilliams, Martin and Liu, Zhaoyuan
                      and Ginhoux, Florent and Beyer, Marc D and Thiele, Christoph
                      and Meissner, Felix and Hasenauer, Jan and Wachten, Dagmar
                      and Mass, Elvira},
      title        = {{K}upffer cell programming by maternal obesity triggers
                      fatty liver disease.},
      journal      = {Nature},
      volume       = {644},
      number       = {8077},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DZNE-2025-00972},
      pages        = {790 - 798},
      year         = {2025},
      abstract     = {Kupffer cells (KCs) are tissue-resident macrophages that
                      colonize the liver early during embryogenesis1. Upon liver
                      colonization, KCs rapidly acquire a tissue-specific
                      transcriptional signature, mature alongside the developing
                      liver and adapt to its functions1-3. Throughout development
                      and adulthood, KCs perform distinct core functions that are
                      essential for liver and organismal homeostasis, including
                      supporting fetal erythropoiesis, postnatal erythrocyte
                      recycling and liver metabolism4. 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 neonate mice born to obese mothers, followed by
                      replenishment with naive monocytes, rescues fatty liver
                      disease. Furthermore, genetic ablation of the gene encoding
                      hypoxia-inducible factor-α (HIF1α) 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 diseases5.},
      keywords     = {Animals / Kupffer Cells: metabolism / Kupffer Cells:
                      pathology / Kupffer Cells: cytology / Female / Mice /
                      Pregnancy / Hypoxia-Inducible Factor 1, alpha Subunit:
                      genetics / Hypoxia-Inducible Factor 1, alpha Subunit:
                      metabolism / Hypoxia-Inducible Factor 1, alpha Subunit:
                      deficiency / Pregnancy in Obesity: pathology / Pregnancy in
                      Obesity: metabolism / Fatty Liver: pathology / Fatty Liver:
                      etiology / Fatty Liver: metabolism / Male / Liver:
                      metabolism / Liver: pathology / Liver: embryology / Liver:
                      cytology / Glycolysis / Hepatocytes: metabolism / Animals,
                      Newborn / Disease Models, Animal / Oxidative Phosphorylation
                      / Prenatal Exposure Delayed Effects: pathology / Mice,
                      Inbred C57BL / Macrophages: metabolism / Obesity:
                      complications / Hypoxia-Inducible Factor 1, alpha Subunit
                      (NLM Chemicals) / Hif1a protein, mouse (NLM Chemicals)},
      cin          = {AG Schultze / AG Beyer / PRECISE},
      ddc          = {500},
      cid          = {I:(DE-2719)1013038 / I:(DE-2719)1013035 /
                      I:(DE-2719)1013031},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 351
                      - Brain Function (POF4-351) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-351 /
                      G:(DE-HGF)POF4-352},
      experiment   = {EXP:(DE-2719)PRECISE-20190321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40533564},
      pmc          = {pmc:PMC12367551},
      doi          = {10.1038/s41586-025-09190-w},
      url          = {https://pub.dzne.de/record/280788},
}