Journal
PLOS COMPUTATIONAL BIOLOGY
Volume 18, Issue 9, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1010469
Keywords
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Funding
- Swedish Research Council [2018-05418, 2018-03319, 2020-04826, 2014-6157]
- CENIIT [15.09]
- Swedish Foundation for Strategic Research [ITM17-0245]
- SciLifeLab National COVID-19 Research Programme - Knut and Alice Wallenberg Foundation [2020.0182]
- Swedish Fund for Research without Animal Experiments [F2019-0010]
- ELLIIT [2020A12]
- VINNOVA [2020-04711]
- Swedish Fund for Research without Animal Experiments
- Swedish Research Council
- H2020 project PRECISE4Q [777107]
- Swedish Foundation for Strategic Research (SSF) [ITM17-0245] Funding Source: Swedish Foundation for Strategic Research (SSF)
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There is currently significant interest in diets with new combinations of macronutrients and fasting schedules. However, there is a lack of consensus on the impact of these diets due to differing variables measured in different populations. This study presents a tool that uses a mathematical model to integrate and explain data from multiple clinical studies, accurately predicting new data and allowing for personalized metabolic responses.
Today, there is great interest in diets proposing new combinations of macronutrient compositions and fasting schedules. Unfortunately, there is little consensus regarding the impact of these different diets, since available studies measure different sets of variables in different populations, thus only providing partial, non-connected insights. We lack an approach for integrating all such partial insights into a useful and interconnected big picture. Herein, we present such an integrating tool. The tool uses a novel mathematical model that describes mechanisms regulating diet response and fasting metabolic fluxes, both for organ-organ crosstalk, and inside the liver. The tool can mechanistically explain and integrate data from several clinical studies, and correctly predict new independent data, including data from a new study. Using this model, we can predict non-measured variables, e.g. hepatic glycogen and gluconeogenesis, in response to fasting and different diets. Furthermore, we exemplify how such metabolic responses can be successfully adapted to a specific individual's sex, weight, height, as well as to the individual's historical data on metabolite dynamics. This tool enables an offline digital twin technology.
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