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Glucagon contributes to liver zonation.

ABSTRACT: Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/β-catenin. The glucagon and Wnt/β-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counterplay with the Wnt/β-catenin signaling pathway.

SUBMITTER: Cheng X

PROVIDER: S-EPMC5924920 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Glucagon contributes to liver zonation.

Cheng Xiping X Kim Sun Y SY Okamoto Haruka H Xin Yurong Y Yancopoulos George D GD Murphy Andrew J AJ Gromada Jesper J

Proceedings of the National Academy of Sciences of the United States of America 20180319 17

Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes we ...[more]

PMID: 29555772

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