A continuum receptor model of hepatic lipoprotein metabolism

Tindall, Marcus J.; Wattis, Jonathan A. D.; O’Malley, Brendan; Pickersgill, Laura; Jackson, Kim G.

doi:10.1016/j.jtbi.2008.11.016

Cited by 19 publications

(32 citation statements)

References 18 publications

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“…A more in-depth model of VLDL assembly has been proposed by Shorten and Upreti [50] in which the lipid composition of secreted VLDLs can be determined from uptake of individual free fatty acids after elongation and desaturation by liver enzymes. Another area of mathematical modelling is the hepatic uptake and metabolism of lipoproteins, and the competition between subclasses within this process [46,58].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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The aim of this paper is to develop a mathematical model capable of simulating the metabolic response to a variety of mixed meals in fed and fasted conditions with particular emphasis placed on the hepatic triglyceride element of the model. Model validation is carried out using experimental data for the ingestion of three mixed composition meals over a 24-hour period. Comparison with experimental data suggests the model predicts key plasma lipids accurately given a prescribed insulin profile. One counter-intuitive observation to arise from simulations is that liver triglyceride initially decreases when a high fat meal is ingested, a phenomenon potentially explained by the carbohydrate portion of the meal raising plasma insulin.

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Section: Introductionmentioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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“…Our work here couples the endocytosis model of VLDL and LDL metabolism in an hepatocyte described in [15] with the description of cholesterol biosynthesis detailed in [10] and extends it with descriptions of LDLR synthesis, VLDL uptake and VLDL to LDL delipidation. An overview of the main processes included in our model is given in Figure 1 with further details on the exact mechanisms provided in Figure 2.…”

Section: Cholesterol Biosynthesis and Lipoprotein Metabolismmentioning

confidence: 99%

“…In this work we present a model of integrated cholesterol biosynthesis, which includes a description of SREBP-2 regulation by cholesterol (as detailed in [14]), a full description of VLDL and LDL uptake (as detailed in [15]) coupled with a description of receptor biosynthesis. The work provides a full account of model formulation, analysis and testing thereof.…”

Section: Introductionmentioning

confidence: 99%

“…Because of this we have included VLDL to LDL delipidation in this model in order to explore it's effects without the complication of a full description of dietary lipoprotein metabolism. Finally, we wish to evaluate any differences that the assumption of a continuum of receptors on the surface of a cell has (as per [15]) versus that of discrete description of receptors bound by differing numbers of VLDL and LDL particles (as per [13]). …”

Section: Introductionmentioning

confidence: 99%

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An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism

2018

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Abstract:Cholesterol regulation is an important aspect of human health. In this work we bring together and extend two recent mathematical models describing cholesterol biosynthesis and lipoprotein endocytosis to create an integrated model of lipoprotein metabolism in the context of a single hepatocyte. The integrated model includes a description of low density lipoprotein (LDL) receptor and cholesterol synthesis, delipidation of very low density lipoproteins (VLDLs) to LDLs and subsequent lipoprotein endocytosis. Model analysis shows that cholesterol biosynthesis produces the majority of intracellular cholesterol. The availability of free receptors does not greatly effect the concentration of intracellular cholesterol, but has a detrimental effect on extracellular VLDL and LDL levels. We test our model by considering its ability to reproduce the known biology of Familial Hypercholesterolaemia and statin therapy. In each case the model reproduces the known biological behaviour. Quantitative differences in response to statin therapy are discussed in the context of the need to extend the work to a more in vivo setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of in silico models of lipoprotein metabolism.

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“…There are also models focusing on the metabolism of a variety of lipoproteins in the body and the transport of and conversion between them [30]. Other models describe specific types of lipoprotein and their competitive uptake in the liver [31][32][33]. Models of skeletal muscle metabolism, particularly in terms of energy balance, have also been proposed [34,35] however these are restricted to skeletal muscle and ignore the rest of the body.…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of the Human Metabolic System and Metabolic Flexibility

et al. 2014

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Abstract In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the post prandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin, and insulin-resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility.In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare.

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A continuum receptor model of hepatic lipoprotein metabolism

Cited by 19 publications

References 18 publications

Mathematical modelling of hepatic lipid metabolism

Mathematical modelling of hepatic lipid metabolism

An Integrated Mathematical Model of Cellular Cholesterol Biosynthesis and Lipoprotein Metabolism

A Mathematical Model of the Human Metabolic System and Metabolic Flexibility

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