2019
DOI: 10.1002/hep.30221
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Hepatic Zonation Now on Hormones!

Abstract: The liver plays important roles in maintaining systemic metabolic homeostasis, but our understanding of how the liver coordinates such a wide range of functions is still evolving. A recent study led by Dr. Gromada advanced the knowledge of the regulators for liver zonation with the discovery of a novel role for glucagon as a liver metabolic zonation regulator utilizing Glucagon (gcg) KO mice combined with RNA sequencing and in situ hybridization (ISH) (1). The established mechanism of metabolic liver zonation … Show more

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Cited by 6 publications
(5 citation statements)
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References 9 publications
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“…We and others have established that Wnt signaling is a fundamental regulator of hepatic zonation by controlling zone-specific gene expression [8][9][10][11]. Consistent with this, Wnt signaling is zone-dependent and follows the metabolic gradient, activating gene expression in pericentral hepatocytes (zone 3), while suppressing genes in its periportal counterparts (zone 1).…”
Section: Introductionsupporting
confidence: 53%
“…We and others have established that Wnt signaling is a fundamental regulator of hepatic zonation by controlling zone-specific gene expression [8][9][10][11]. Consistent with this, Wnt signaling is zone-dependent and follows the metabolic gradient, activating gene expression in pericentral hepatocytes (zone 3), while suppressing genes in its periportal counterparts (zone 1).…”
Section: Introductionsupporting
confidence: 53%
“…Such compartmentalization not only allows for the functional partition of labor but also restricts particular toxicant-mediated injuries to specific zones, allowing surviving cells in other zones to repair the liver (154). Moreover, to maintain systemic metabolic homeostasis, mammalian hepatic zonation and the heterogeneity of HC gene expression are tightly regulated by various physiological factors and signaling pathways, such as the Wnt/β-catenin pathway, which is considered one of the master regulators of hepatic zonation (92,155,156). The lack of hepatic zonation in the zebrafish liver means that findings relevant to understanding zebrafish liver regeneration may not be able to be extrapolated to higher vertebrates.…”
Section: Biliary Epithelial Cell-derived Liver Progenitor Cell-mediated Regeneration In the Zebrafish Model Systemmentioning
confidence: 99%
“…125 The hepatic artery provides oxygenrich blood and the portal vein provides deoxygenated and nutrient-rich blood originating from the intestines. 122 Both blood flows are mixed and the composition of the blood changes continuously in its concentration of, amongst other, oxygen, 131,132 ammonia, glucose and some hormones 133 such as insulin and glucagon throughout its path through the hepatic lobule due to the metabolic activity of the hepatocytes, leading to zonation. Hence, the specific function and phenotype of the hepatocytes depends on the blood composition they are exposed to and by consequence to their specific location 134 (called zone) in the hepatic lobule.…”
Section: Liver Anatomymentioning
confidence: 99%