Mathematical Modeling of Dietary Timing- and Protein Quality-Responsive Liver Circadian Clock and its Function on Ribosome Biogenesis

Lu L, Levy JL, Anthony TG, Androulakis IP · 2026 · Physiological Genomics · Atlas ID LU2026

What this study shows

Builds a semi-mechanistic model in which liver mTORC1 and GCN2-ISR signalling are driven by RHYTHMS in dietary essential amino acid availability rather than by a fixed nutrient level. Simulations show the two pathways jointly set metabolic entrainability and are required to keep the peripheral clock and ribosome biogenesis synchronised under nutrient stress, and predict individualised recovery trajectories after a transient dietary disruption. A worked example of treating mTORC1 activity as a time-varying pattern whose shape — not just its average — determines the downstream growth output.

Abstract

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Independent of the suprachiasmatic nucleus, peripheral clocks can be strongly entrained by dietary signals. Although feeding time has been widely studied, the effects of food quality-particularly nutrient availability and stress-on peripheral circadian entrainment and metabolic regulation remain less understood. We developed a semi-mechanistic mathematical model of peripheral clock synchronization and clock-controlled ribosome biogenesis (RiBi) in response to feeding/fasting cycles and rhythms in dietary essential amino acid (EAA) availability.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Semi-mechanistic computational model of mammalian liver (peripheral clock, mTORC1, GCN2-ISR, ribosome biogenesis)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Semi-mechanistic computational model of mammalian liver (peripheral clock, mTORC1, GCN2-ISR, ribosome biogenesis)
Journal	Physiological Genomics
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1152/physiolgenomics.00152.2026 · PMID 42647400

Extracted findings

Intervention	In silico feeding/fasting schedules and dietary essential amino acid rhythms; simulated GCN2-ISR modulation
Target	mTORC1 and GCN2-ISR; clock-controlled ribosome biogenesis
Model	Computational model (mammalian liver)
Effect	Timing and quality of amino acid intake, not average level, set circadian entrainment and ribosome biogenesis dynamics

Cite this paper

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Lu, L., Levy, J. L., Anthony, T. G., & Androulakis, I. P. (2026). Mathematical Modeling of Dietary Timing- and Protein Quality-Responsive Liver Circadian Clock and its Function on Ribosome Biogenesis. Physiological Genomics. https://doi.org/10.1152/physiolgenomics.00152.2026

@article{LU2026,
  author       = {Lu, L. and Levy, J. L. and Anthony, T. G. and Androulakis, I. P.},
  title        = {{Mathematical Modeling of Dietary Timing- and Protein Quality-Responsive Liver Circadian Clock and its Function on Ribosome Biogenesis}},
  journal      = {Physiological Genomics},
  year         = {2026},
  doi          = {10.1152/physiolgenomics.00152.2026},
  note         = {PMID: 42647400},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LU2026) [Data set]. https://mtor-atlas.org/study/LU2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LU2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LU2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LU2026/},
  doi          = {10.5281/zenodo.22059963}
}