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Metabolic zonation of the liver: Regulation and implications for liver function
Abstract
Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the various metabolic pathways and functions forms the basis for the efficient adaptation of liver metabolism to the different nutritional requirements of the whole organism in different metabolic states. The present review summarizes current knowledge about this heterogeneity, its development and determination, as well as about its significance for the understanding of all aspects of liver function and pathology, especially of intermediary metabolism, biotransformation of drugs and zonal toxicity of hepatotoxins.
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“For example, hepatocytes in zone 1 are more involved in gluconeogenesis and beta-oxidation, reflecting the relatively oxygen- and nutrient-rich environment near the portal vein and hepatic artery, whereas hepatocytes in zone 3 are more active in glycolysis and lipogenesis, reflecting the depletion of oxygen and nutrients near the central vein3,4,6.”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]
In the citing paper
“Within the lobule, hepatocytes are classically organized into three zones, with zone 1 proximal to the portal vein and hepatic artery, zone 3 proximal to the central vein, and zone 2 in the intermediate region3,4.”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]
In the citing paper
“For example, hepatocytes in zone 1 are more involved in gluconeogenesis and beta-oxidation, reflecting the relatively oxygen- and nutrient-rich environment near the portal vein and hepatic artery, whereas hepatocytes in zone 3 are more active in glycolysis and lipogenesis, reflecting the depletion of oxygen and nutrients near the central vein3,4,6.”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [3]
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Metadata
- Authors
- Gebhardt, R.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Gebhardt, Rolf
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 1992-01
- Volume
- 53
- Issue
- 3
- Pages
- 275-354
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W2061717797
- Cited by
- 607
- References
- 880
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 16 · 2023: 30 · 2022: 22 · 2021: 31 · 2020: 33 · 2019: 30 · 2018: 29 · 2017: 19 · 2016: 18 · 2015: 15 · 2014: 19 · 2013: 21 · 2012: 15
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- metabolic zonation, liver lobule, hepatocyte heterogeneity, intermediary metabolism, drug metabolism, hepatotoxins, liver function, liver pathology
- MeSH terms
- Animals, Humans, Liver
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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