ArticleNature metabolism2025
Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- The Spatial Redox-Metalloptosis Axis in Liver Disease: A Hypothesis on Regional Susceptibility to Ferroptosis and Cuproptosis.Antioxidants (Basel, Switzerland) · 2026Review
- Regulation and clinical manifestations of gluconeogenesis dysfunction.npj metabolic health and disease · 2026Review
- Article
- [Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- A novel subset of hepatocytes is simultaneously gluconeogenic andbioRxiv : the preprint server for biology · 2026Article
- Review
- Spatial protein gradients pattern liver metabolism.Nature metabolism · 2026Article
- CellUntangler: Separating distinct biological signals in single-cell data with deep generative models.Cell genomics · 2026Article
- Spatial immune dysregulation in MASLD: integration of lobular zoning, metabolism and immune function.Frontiers in immunology · 2026Review
- Article
- Widespread discordance between mRNA expression, protein abundance andbioRxiv : the preprint server for biology · 2025Article
- Mitochondria Metabolism Regulates Glucose-Lipid Homeostasis in Neurodegenerative Diseases.Research (Washington, D.C.) · 2025Review
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13 authors.
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Abstract
Hepatocytes are organized along a spatial axis between the portal triad and the central vein to form functionally repetitive units known as lobules. The hepatocytes perform distinct metabolic functions depending on their location within the lobule. Single-cell analysis of hepatocytes across the liver lobule demonstrates that gluconeogenic gene expression is relatively low in the fed state and gradually increases in the periportal hepatocytes during the initial fasting period. As fasting progresses, pericentral hepatocyte gluconeogenic gene expression and gluconeogenic activity also increase and, following entry into a starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression and activity to the periportal hepatocytes. In parallel, starvation suppresses canonical β-catenin signalling and modulates the expression of pericentral and periportal glutamine synthetase and glutaminase, respectively, resulting in enhanced incorporation of glutamine into glucose. Thus, hepatocyte gluconeogenic gene expression and glucose production are spatially and temporally plastic across the liver lobule, underscoring the complexity of defining hepatic insulin resistance and glucose production on a whole-organ level, as well as for a particular fasted or fed condition.
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