TY - JOUR
T1 - Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer
AU - Clasen, Frederick
AU - Nunes, Patrícia M.
AU - Bidkhori, Gholamreza
AU - Bah, Nourdine
AU - Boeing, Stefan
AU - Shoaie, Saeed
AU - Anastasiou, Dimitrios
N1 - Funding Information:
We thank all members of the D.A. and S.S. laboratories for valuable discussions and input throughout this work. We acknowledge the Crick Advanced Sequencing Science Technology Platform for RNA-sequencing, and the Crick Metabolomics Science Technology Platform, particularly Paul Driscoll and James Ellis, for useful discussions and support with metabolic measurements. We are also grateful to the Crick Biological Research Facility and in vivo Imaging Science Technology Platform for their technical support. This work was funded by the Engineering and Physical Sciences Research Council (EPSRC, EP/S001301/1), the Biotechnology Biological Sciences Research Council (BBSRC, BB/S016899/1) and Science for Life Laboratory to S.S. by the MRC (MC_UP_1202/1) to D.A. and by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2113), the UK Medical Research Council (CC2113) and the Wellcome Trust (CC2113) to D.A. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Conceptualization, F.C. S.S. and D.A.; Methodology, F.C. P.M.N. S.S. and D.A.; Software, F.C. and G.B.; Formal analysis, F.C. and P.M.N.; Investigation, F.C. and P.M.N.; Resources, G.B. N.B. and S.B.; Writing – Original Draft, F.C. and D.A.; Writing – Review and Editing, F.C. S.S. and D.A.; Supervision, S.S. and D.A.; Project administration, D.A.; Funding acquisition, S.S. and D.A. The authors declare no competing interests.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/2/17
Y1 - 2023/2/17
N2 - 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.
AB - 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.
KW - Biological sciences
KW - Cancer
KW - Cellular physiology
KW - Physiology
UR - http://www.scopus.com/inward/record.url?scp=85148027045&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106040
DO - 10.1016/j.isci.2023.106040
M3 - Article
AN - SCOPUS:85148027045
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 2
M1 - 106040
ER -
