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<lom:identifier>
  
<lom:catalog>DOI</lom:catalog>

  
<lom:entry>
  
<lom:langstring xml:lang="x-none">10.1038/s41586-025-09190-w</lom:langstring>

  
</lom:entry>

  
</lom:identifier>

  
<lom:title>
  
<lom:langstring xml:lang="en">Kupffer cell programming by maternal obesity triggers fatty liver disease</lom:langstring>

  
</lom:title>

  
<lom:description>
  
<lom:langstring xml:lang="en">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 functions. 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 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 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 diseases.</lom:langstring>

  
</lom:description>

  
<lom:language>eng</lom:language>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Haematopoiesis</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Innate immunity</lom:langstring>

  
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<lom:datetime>2026-02-12T08:53:11.222Z</lom:datetime>

  
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<lom:langstring xml:lang="x-none">Author</lom:langstring>

  
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<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Huang;Hao;
FN:Hao Huang
X-ORCID:https://orcid.org/0000-0003-3878-3947
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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VERSION:3.0
N:Splichalova;Iva;
FN:Iva Splichalova
END:VCARD</lom:vcard>

  
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VERSION:3.0
N:Blank-Stein;Nelli;
FN:Nelli Blank-Stein
END:VCARD</lom:vcard>

  
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VERSION:3.0
N:Viola;Maria Francesca;
FN:Maria Francesca Viola
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END:VCARD</lom:vcard>

  
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<lom:centity>
  
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VERSION:3.0
N:Franco Taveras;Eliana;
FN:Eliana Franco Taveras
X-ORCID:https://orcid.org/0009-0009-2227-6765
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Acil;Kerim;
FN:Kerim Acil
X-ORCID:https://orcid.org/0009-0002-7838-9928
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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N:Fink;Diana;
FN:Diana Fink
X-ORCID:https://orcid.org/0009-0008-1572-4390
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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VERSION:3.0
N:Petrovic;Franzisca;
FN:Franzisca Petrovic
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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VERSION:3.0
N:Makdissi;Nikola;
FN:Nikola Makdissi
X-ORCID:https://orcid.org/0000-0002-9345-038X
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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VERSION:3.0
N:Bayar;Seyhmus;
FN:Seyhmus Bayar
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N:Mauel;Katharina;
FN:Katharina Mauel
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END:VCARD</lom:vcard>

  
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N:Radwaniak;Carolin;
FN:Carolin Radwaniak
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END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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N:Zurkovic;Jelena;
FN:Jelena Zurkovic
X-ORCID:https://orcid.org/0000-0002-5932-4849
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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N:Kayvanjoo;Amir H.;
FN:Amir H. Kayvanjoo
X-ORCID:https://orcid.org/0000-0003-1315-8336
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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N:Wunderling;Klaus;
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N:Jessen;Malin;
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END:VCARD</lom:vcard>

  
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<lom:centity>
  
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N:Yaghmour;Mohamed H.;
FN:Mohamed H. Yaghmour
END:VCARD</lom:vcard>

  
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<lom:centity>
  
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VERSION:3.0
N:Kenner;Lukas;
FN:Lukas Kenner
X-ORCID:https://orcid.org/0000-0003-2184-1338
END:VCARD</lom:vcard>

  
</lom:centity>

  
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N:Ulas;Thomas;
FN:Thomas Ulas
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END:VCARD</lom:vcard>

  
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N:Grein;Stephan;
FN:Stephan Grein
X-ORCID:https://orcid.org/0000-0001-9524-6633
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Schultze;Joachim L.;
FN:Joachim L. Schultze
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
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VERSION:3.0
N:Scott;Charlotte L.;
FN:Charlotte L. Scott
X-ORCID:https://orcid.org/0000-0003-4914-6580
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Guilliams;Martin;
FN:Martin Guilliams
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Liu;Zhaoyuan;
FN:Zhaoyuan Liu
X-ORCID:https://orcid.org/0000-0002-3117-0833
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
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N:Ginhoux;Florent;
FN:Florent Ginhoux
X-ORCID:https://orcid.org/0000-0002-2857-7755
END:VCARD</lom:vcard>

  
</lom:centity>

  
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VERSION:3.0
N:Beyer;Marc D.;
FN:Marc D. Beyer
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END:VCARD</lom:vcard>

  
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END:VCARD</lom:vcard>

  
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N:Meissner;Felix;
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END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
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N:Hasenauer;Jan;
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END:VCARD</lom:vcard>

  
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N:Wachten;Dagmar;
FN:Dagmar Wachten
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END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
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N:Mass;Elvira;
FN:Elvira Mass
X-ORCID:https://orcid.org/0000-0003-2318-2356
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Balzer;Nora R.;
FN:Nora R. Balzer
END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Seep;Lea;
FN:Lea Seep
X-ORCID:https://orcid.org/0000-0002-0399-1896
END:VCARD</lom:vcard>

  
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<lom:source>
  
<lom:langstring xml:lang="x-none">LOMv1.0</lom:langstring>

  
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