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Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer

Clasen, Frederick; Nunes, Patrícia M; Bidkhori, Gholamreza; Bah, Nourdine; Boeing, Stefan; Shoaie, Saeed; Anastasiou, Dimitrios; (2023) Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer. iScience , 26 (2) , Article 106040. 10.1016/j.isci.2023.106040. Green open access

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Abstract

Dietary nutrient availability and gene expression, together, influence tissue metabolic activity. Here, we explore whether altering dietary nutrient composition in the context of mouse liver cancer suffices to overcome chronic gene expression changes that arise from tumorigenesis and western-style diet (WD). We construct a mouse genome-scale metabolic model and estimate metabolic fluxes in liver tumors and non-tumoral tissue after computationally varying the composition of input diet. This approach, called Systematic Diet Composition Swap (SyDiCoS), revealed that, compared to a control diet, WD increases production of glycerol and succinate irrespective of specific tissue gene expression patterns. Conversely, differences in fatty acid utilization pathways between tumor and non-tumor liver are amplified with WD by both dietary carbohydrates and lipids together. Our data suggest that combined dietary component modifications may be required to normalize the distinctive metabolic patterns that underlie selective targeting of tumor metabolism.

Type: Article
Title: Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2023.106040
Publisher version: http://dx.doi.org/10.1016/j.isci.2023.106040
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Biological sciences; Physiology; Cellular physiology; Cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10185827
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