University of Oulu

Thomas Kietzmann, Metabolic zonation of the liver: The oxygen gradient revisited, Redox Biology, Volume 11, April 2017, Pages 622-630, ISSN 2213-2317,

Metabolic zonation of the liver : the oxygen gradient revisited

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Author: Kietzmann, Thomas1
Organizations: 1Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Elsevier, 2017
Publish Date: 2017-02-27


The liver has a multitude of functions which are necessary to maintain whole body homeostasis. This requires that various metabolic pathways can run in parallel in the most efficient manner and that futile cycles are kept to a minimum. To a large extent this is achieved due to a functional specialization of the liver parenchyma known as metabolic zonation which is often lost in liver diseases. Although this phenomenon is known for about 40 years, the underlying regulatory pathways are not yet fully elucidated. The physiologically occurring oxygen gradient was considered to be crucial for the appearance of zonation; however, a number of reports during the last decade indicating that β-catenin signaling, and the hedgehog (Hh) pathway contribute to metabolic zonation may have shifted this view. In the current review we connect these new observations with the concept that the oxygen gradient within the liver acinus is a regulator of zonation. This is underlined by a number of facts showing that the β-catenin and the Hh pathway can be modulated by the hypoxia signaling system and the hypoxia-inducible transcription factors (HIFs). Altogether, we provide a view by which the dynamic interplay between all these pathways can drive liver zonation and thus contribute to its physiological function.

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Series: Redox biology
ISSN: 2213-2317
ISSN-E: 2213-2317
ISSN-L: 2213-2317
Volume: 11
Issue: April
Pages: 622 - 630
DOI: 10.1016/j.redox.2017.01.012
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: The authors is grateful to all researchers who contributed to the field and apologizes to all those whose work could not be cited due to space limitations. The work was supported by grants from the Academy of Finland (SA 296027), Jane and Aatos Erkko Foundation, Biocenter Oulu, and the European Cooperation in Science and Technology Organization (COST Action BM1203/EU‐ROS).
Academy of Finland Grant Number: 296027
Detailed Information: 296027 (Academy of Finland Funding decision)
Copyright information: This is an open access article under the CC BY-NC-ND license (