2026-04-29T07:23:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/200342024-09-27T08:26:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Plata-Gómez, Ana Belén author de Prado-Rivas, Lucía author Sanz, Alba author Deleyto-Seldas, Nerea author García, Fernando author de la Calle Arregui, Celia author Silva, Camila author Caleiras, Eduardo author Graña-Castro, Osvaldo author Piñeiro-Yáñez, Elena author Krebs, Joseph author Leiva-Vega, Luis author Muñoz, Javier author Jain, Ajay author Sabio, Guadalupe author Efeyan, Alejo author 2024-03-18 The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/β-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program. Nat Commun. 2024 Mar 18;15(1):1878. http://hdl.handle.net/20.500.12105/20034 38499523 10.1038/s41467-024-46032-1 2041-1723 Nature communications Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.