2026-04-29T07:22:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/200342024-09-27T08:26:57Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación La Caixa
2024-07-03T14:16:41Z
2024-07-03T14:16:41Z
2024-03-18
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
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.
eng
Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.
journal article
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URL
https://repisalud.isciii.es/bitstreams/cc67fa07-b66f-490d-ad44-2caa1811de73/download
File
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Hepatic nutrient and hormone_Nat Commun_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/cae398c5-a7df-4d77-8748-273db69ee300/download
File
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Hepatic nutrient and hormone_Nat Commun_2024.pdf.txt