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000284345 037__ $$aDZNE-2026-00116
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000284345 1001_ $$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$$c2026
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000284345 520__ $$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.
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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
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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_ $$aBennühr, Bastian$$b4
000284345 7001_ $$aNikolka, Fabian$$b5
000284345 7001_ $$aCheng, Jingyuan$$b6
000284345 7001_ $$aBlank-Stein, Nelli$$b7
000284345 7001_ $$00000-0003-0660-9506$$aViola, Maria Francesca$$b8
000284345 7001_ $$aYaghmour, Mohamed$$b9
000284345 7001_ $$00000-0003-3273-9865$$aArnold, Philipp$$b10
000284345 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b11
000284345 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b12
000284345 7001_ $$00000-0001-5161-2558$$aThiele, Christoph$$b13
000284345 7001_ $$aMeissner, Felix$$b14
000284345 7001_ $$aHiller, Karsten$$b15
000284345 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc D$$b16
000284345 7001_ $$00000-0003-2318-2356$$aMass, Elvira$$b17$$eLast author
000284345 773__ $$0PERI:(DE-600)2007916-3$$a10.1242/dev.204962$$gVol. 153, no. 2, p. dev204962$$n2$$pdev204962$$tDevelopment$$v153$$x0022-0752$$y2026
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