Rozendaal2018 - Model Integrating Glucose and Lipid Dynamics

Model Identifier

MODEL1803200001

Short description

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006145

Format

SBML (L2V4)

Related Publication

In vivo and in silico dynamics of the development of Metabolic Syndrome.
Yvonne J W Rozendaal, Yanan Wang, Yared Paalvast, Lauren L Tambyrajah, Zhuang Li, Ko Willems van Dijk, Patrick C N Rensen, Jan A Kuivenhoven, Albert K Groen, Peter A J Hilbers, Natal A W van Riel
PLoS computational biology , 6/ 2018 , Volume 14 , Issue 6 , pages: e1006145 , PubMed ID: 29879115

Affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.

Abstract: The Metabolic Syndrome (MetS) is a complex, multifactorial disorder that develops slowly over time presenting itself with large differences among MetS patients. We applied a systems biology approach to describe and predict the onset and progressive development of MetS, in a study that combined in vivo and in silico models. A new data-driven, physiological model (MINGLeD: Model INtegrating Glucose and Lipid Dynamics) was developed, describing glucose, lipid and cholesterol metabolism. Since classic kinetic models cannot describe slowly progressing disorders, a simulation method (ADAPT) was used to describe longitudinal dynamics and to predict metabolic concentrations and fluxes. This approach yielded a novel model that can describe long-term MetS development and progression. This model was integrated with longitudinal in vivo data that was obtained from male APOE*3-Leiden.CETP mice fed a high-fat, high-cholesterol diet for three months and that developed MetS as reflected by classical symptoms including obesity and glucose intolerance. Two distinct subgroups were identified: those who developed dyslipidemia, and those who did not. The combination of MINGLeD with ADAPT could correctly predict both phenotypes, without making any prior assumptions about changes in kinetic rates or metabolic regulation. Modeling and flux trajectory analysis revealed that differences in liver fluxes and dietary cholesterol absorption could explain this occurrence of the two different phenotypes. In individual mice with dyslipidemia dietary cholesterol absorption and hepatic turnover of metabolites, including lipid fluxes, were higher compared to those without dyslipidemia. Predicted differences were also observed in gene expression data, and consistent with the emergence of insulin resistance and hepatic steatosis, two well-known MetS co-morbidities. Whereas MINGLeD specifically models the metabolic derangements underlying MetS, the simulation method ADAPT is generic and can be applied to other diseases where dynamic modeling and longitudinal data are available.

Contributors

Submitter of the first revision: Rozendaal YJW
Submitter of this revision: Rahuman S Malik-Sheriff
Modellers: Rozendaal YJW, Rahuman S Malik-Sheriff

Metadata information

is (1 statement)

BioModels Database MODEL1803200001

isDescribedBy (1 statement)

PubMed 29879115

Curation status

Non-curated

Connected external resources

SBGN view in Newt Editor

Name	Description	Size	Actions
Model files (1)
modelYR2017.xml	SBML L2V4 representation of Rozendaal2018 - MINGLeD	128.75 KB	Preview \| Download

Model originally submitted by : Rozendaal YJW
Submitted: Feb 7, 2019 3:50:21 PM
Last Modified: Feb 7, 2019 3:50:21 PM

Revisions

Version: 4
- Submitted on: Feb 7, 2019 3:50:21 PM
- Submitted by: Rahuman S Malik-Sheriff
- With comment: Edited model metadata online.