Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer
Summary: 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 wester...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223001177 |
| _version_ | 1797903303084867584 |
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| author | Frederick Clasen Patrícia M. Nunes Gholamreza Bidkhori Nourdine Bah Stefan Boeing Saeed Shoaie Dimitrios Anastasiou |
| author_facet | Frederick Clasen Patrícia M. Nunes Gholamreza Bidkhori Nourdine Bah Stefan Boeing Saeed Shoaie Dimitrios Anastasiou |
| author_sort | Frederick Clasen |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-10T09:30:44Z |
| format | Article |
| id | doaj.art-38b6642d57c14c0a9263e5c1585f8e4a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:30:44Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-38b6642d57c14c0a9263e5c1585f8e4a2023-02-19T04:27:02ZengElsevieriScience2589-00422023-02-01262106040Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancerFrederick Clasen0Patrícia M. Nunes1Gholamreza Bidkhori2Nourdine Bah3Stefan Boeing4Saeed Shoaie5Dimitrios Anastasiou6Cancer Metabolism Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UKCancer Metabolism Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UKBioinformatics and Biostatistics Science Technology Platform, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKBioinformatics and Biostatistics Science Technology Platform, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London SE1 9RT, UK; Science for Life Laboratory (SciLifeLab), KTH - Royal Institute of Technology, Tomtebodavägen 23, 171 65 Solna, Stockholm, Sweden; Corresponding authorCancer Metabolism Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223001177Biological sciencesPhysiologyCellular physiologyCancer |
| spellingShingle | Frederick Clasen Patrícia M. Nunes Gholamreza Bidkhori Nourdine Bah Stefan Boeing Saeed Shoaie Dimitrios Anastasiou Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer iScience Biological sciences Physiology Cellular physiology Cancer |
| title | Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| title_full | Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| title_fullStr | Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| title_full_unstemmed | Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| title_short | Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| title_sort | systematic diet composition swap in a mouse genome scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer |
| topic | Biological sciences Physiology Cellular physiology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223001177 |
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