Bae2017 - Mathematical analysis of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis

  public model
Model Identifier
BIOMD0000001005
Short description
The circadian rhythms influence the metabolic activity from molecular level to tissue, organ, and host level. Disruption of the circadian rhythms manifests to the host's health as metabolic syndromes, including obesity, diabetes, and elevated plasma glucose, eventually leading to cardiovascular diseases. Therefore, it is imperative to understand the mechanism behind the relationship between circadian rhythms and metabolism. To start answering this question, we propose a semimechanistic mathematical model to study the effect of circadian disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark cycle and feeding-fasting cycle as two environmental inputs that entrain the metabolic activity in the liver. The model was validated by comparison with data from mice and rat experimental studies. Formal sensitivity and uncertainty analyses were conducted to elaborate on the driving forces for hepatic gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout suggests that modification to the local pathways tied most closely to the feeding-fasting rhythms may be the most efficient way to restore the disrupted glucose metabolism in liver.
Format
SBML (L2V4)
Related Publication
  • Mathematical analysis of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis: the intertwining entraining roles of light and feeding.
  • Bae SA, Androulakis IP
  • American journal of physiology. Endocrinology and metabolism , 6/ 2018 , Volume 314 , Issue 6 , pages: E531-E542 , PubMed ID: 29351477
  • Chemical & Biochemical Engineering Department, Rutgers University , Piscataway, New Jersey.
  • The circadian rhythms influence the metabolic activity from molecular level to tissue, organ, and host level. Disruption of the circadian rhythms manifests to the host's health as metabolic syndromes, including obesity, diabetes, and elevated plasma glucose, eventually leading to cardiovascular diseases. Therefore, it is imperative to understand the mechanism behind the relationship between circadian rhythms and metabolism. To start answering this question, we propose a semimechanistic mathematical model to study the effect of circadian disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark cycle and feeding-fasting cycle as two environmental inputs that entrain the metabolic activity in the liver. The model was validated by comparison with data from mice and rat experimental studies. Formal sensitivity and uncertainty analyses were conducted to elaborate on the driving forces for hepatic gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout suggests that modification to the local pathways tied most closely to the feeding-fasting rhythms may be the most efficient way to restore the disrupted glucose metabolism in liver.
Contributors
Ashok Palaniappan, Kausthubh Ramachandran

Metadata information

hasTaxon
Taxonomy Mus musculus
Taxonomy Rattus norvegicus
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
C39030
isDescribedBy

Curation status
Curated


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Model files

Bae2018.xml SBML L2V4 file of ODE model of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis 304.56 KB Preview | Download

Additional files

Bae2018.omex COMBINE archive of ODE model of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis 35.22 KB Preview | Download
Bae2018.sedml SED-ML file of ODE model of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis 23.96 KB Preview | Download
Bae2018.cps COPASI 4.30 (Build 240) of ODE model of circadian disruption and metabolic re-entrainment of hepatic gluconeogenesis 370.64 KB Preview | Download

  • Model originally submitted by : Ashok Palaniappan
  • Submitted: 08-Apr-2021 00:54:46
  • Last Modified: 08-Apr-2021 00:54:46
Revisions
  • Version: 3 public model Download this version
    • Submitted on: 08-Apr-2021 00:54:46
    • Submitted by: Kausthubh Ramachandran
    • With comment: Automatically added model identifier BIOMD0000001005
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Curator's comment:
(added: 08 Apr 2021, 00:40:05, updated: 08 Apr 2021, 00:53:25)
Simulation was performed using COPASI 4.30 (Build 240) and the Figs 2A and 2D were generated using Excel 2010. It should be noted that the simulation performed by the modelers is unable to exactly reproduce the other figures in the original publication. The simulation is able to generate graphs which follow the same oscillatory trends as the figures in the publication. But, the generated graphs differ in characteristics like amplitude from the figures in the original publication. The reason(s) why two of the figures are reproducible while the other figures aren't working are not understood. For further details regarding how to use or reuse the files in this submission, please contact the submitters directly with the details as given in the submitted files.