Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.

ABSTRACT: 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 recapitulate

SUBMITTER: Plata-Gomez AB 

PROVIDER: S-EPMC10948770 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature