Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20034
Título
Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.
Autor(es)
Plata-Gómez, Ana Belén | de Prado-Rivas, Lucía | Sanz, Alba | Deleyto-Seldas, Nerea | García, Fernando | de la Calle Arregui, Celia | Silva, Camila | Caleiras, Eduardo | Graña-Castro, Osvaldo CNIO | Piñeiro-Yáñez, Elena | Krebs, Joseph | Leiva-Vega, Luis CNIC | Muñoz, Javier | Jain, Ajay | Sabio, Guadalupe CNIC | Efeyan, Alejo CNIO
Fecha de publicación
2024-03-18
Cita
Nat Commun. 2024 Mar 18;15(1):1878.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Endothelial Cells | Liver | Swine | Animals | Mechanistic Target of Rapamycin Complex 1 | Hepatocytes | Signal Transduction | Insulin
Versión en línea
DOI
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