000284345 001__ 284345 000284345 005__ 20260129104141.0 000284345 0247_ $$2doi$$a10.1242/dev.204962 000284345 0247_ $$2pmid$$apmid:41459815 000284345 0247_ $$2ISSN$$a0022-0752 000284345 0247_ $$2ISSN$$a0950-1991 000284345 0247_ $$2ISSN$$a1477-9129 000284345 037__ $$aDZNE-2026-00116 000284345 041__ $$aEnglish 000284345 082__ $$a570 000284345 1001_ $$0P:(DE-2719)9002664$$aMakdissi, Nikola$$b0$$udzne 000284345 245__ $$aKupffer cells control neonatal hepatic metabolism via Igf1 signaling. 000284345 260__ $$aCambridge$$bThe Company of Biologists$$c2026 000284345 3367_ $$2DRIVER$$aarticle 000284345 3367_ $$2DataCite$$aOutput Types/Journal article 000284345 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1769679514_4633 000284345 3367_ $$2BibTeX$$aARTICLE 000284345 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000284345 3367_ $$00$$2EndNote$$aJournal Article 000284345 520__ $$aDuring perinatal development, liver metabolism is tightly regulated to ensure energy supply for the newborn. Before birth, glycogen is stored in hepatocytes and later metabolized to glucose, meeting neonatal energy demands. Shortly after birth, lipogenesis begins, driven by transcriptional activation of enzymes involved in fatty acid oxidation. These processes are thought to be largely regulated by systemic insulin and glucagon levels. However, the role of liver-derived local factors in neonatal hepatocyte metabolism remains unexplored. Kupffer cells (KCs), the liver's resident macrophages, colonize the fetal liver early in embryogenesis and support liver metabolism in adulthood. Yet whether KCs influence neonatal hepatocyte metabolism is unknown. Using conditional knockout mouse models targeting macrophages, we demonstrate that yolk sac-derived KCs play a crucial role in hepatocyte glycogen storage and function by regulating the tricarboxylic acid cycle, a role monocyte-derived KC-like cells cannot substitute. Newborn pups lacking yolk sac-derived KCs mobilize glycogen more rapidly, a process in part regulated by insulin-like growth factor 1 (Igf1) production. Our findings identify KCs as major source of Igf1, with local production essential for balanced hepatocyte metabolism at birth. 000284345 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000284345 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x1 000284345 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x2 000284345 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000284345 650_7 $$2Other$$aHepatocytes 000284345 650_7 $$2Other$$aIgf1 000284345 650_7 $$2Other$$aKupffer cell 000284345 650_7 $$2Other$$aLiver development 000284345 650_7 $$2Other$$aMacrophage 000284345 650_7 $$067763-96-6$$2NLM Chemicals$$aInsulin-Like Growth Factor I 000284345 650_7 $$09005-79-2$$2NLM Chemicals$$aGlycogen 000284345 650_7 $$2NLM Chemicals$$ainsulin-like growth factor-1, mouse 000284345 650_2 $$2MeSH$$aAnimals 000284345 650_2 $$2MeSH$$aInsulin-Like Growth Factor I: metabolism 000284345 650_2 $$2MeSH$$aKupffer Cells: metabolism 000284345 650_2 $$2MeSH$$aKupffer Cells: cytology 000284345 650_2 $$2MeSH$$aLiver: metabolism 000284345 650_2 $$2MeSH$$aLiver: cytology 000284345 650_2 $$2MeSH$$aHepatocytes: metabolism 000284345 650_2 $$2MeSH$$aMice 000284345 650_2 $$2MeSH$$aSignal Transduction 000284345 650_2 $$2MeSH$$aAnimals, Newborn 000284345 650_2 $$2MeSH$$aMice, Knockout 000284345 650_2 $$2MeSH$$aGlycogen: metabolism 000284345 650_2 $$2MeSH$$aYolk Sac: metabolism 000284345 650_2 $$2MeSH$$aYolk Sac: cytology 000284345 650_2 $$2MeSH$$aCitric Acid Cycle 000284345 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE University of Bonn$$x0 000284345 7001_ $$00009-0008-4538-4817$$aHirschmann, Daria J$$b1 000284345 7001_ $$0P:(DE-2719)9002087$$aFrolov, Aleksej$$b2 000284345 7001_ $$0P:(DE-2719)9003270$$aSado, Inaam$$b3$$udzne 000284345 7001_ $$aBennühr, 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