arXiv subjects

Jacob Bendsen

Publications and source records attributed to Jacob Bendsen.

5 recordsLinked to original sources

arXiv2024

A whole-body mathematical model of cholesterol metabolism and transport

Cardiovascular diseases are the leading cause of death. Increased levels of plasma cholesterol are consistently associated with an increased risk of cardiovascular disease. As a result, it is imperative that studies are conducted to determine the best course of action to reduce whole-body cholesterol levels. A whole-body mathematical model for cholesterol metabolism and transport is proposed. The model can simulate the effects of lipid-lowering drugs like statins and anti-PCSK9. The model is based on ordinary differential equations and kinetic functions. It has been validated against literature data. It offers a versatile platform for designing personalized interventions for cardiovascular health management.

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arXiv2024

Modeling principles for a physiology-based whole-body model of human metabolism

Physiological whole-body models are valuable tools for the development of novel drugs where understanding the system aspects is important. This paper presents a generalized model that encapsulates the structure and flow of whole-body human physiology. The model contains vascular, interstitial, and cellular subcompartments for each organ. Scaling of volumes and blood flows is described to allow for investigation across populations or specific patient groups. The model equations and the corresponding parameters are presented along with a catalog of functions that can be used to define the organ transport model and the biochemical reaction model. A simple example illustrates the procedure.

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arXiv2023

Mathematical meal models for simulation of human metabolism

We present and critically discuss five commonly used mathematical models of the meal glucose rate of appearance in humans. Such models are key to simulation of the metabolism in healthy people, people with diabetes, and obese people, and they are central to developing effective treatments and prevention strategies. Furthermore, we discuss important aspects of systematic mathematical modeling of human metabolism, including meal consumption modeling, stoichiometry and reaction kinetics, and general-purpose model components.

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arXiv2023

Quantitative modeling and simulation of biochemical processes in the human body

We present a whole-body model of human metabolism that utilizes a system of organs and blood vessels to simulate the enzymatic reactions. The model focuses on key organs, including the brain, heart and lungs, liver, gut, and kidney, as well as muscle and adipose tissue. The model equations are formulated using stoichiometry and Michaelis-Menten kinetics to describe the enzymatic reactions. We demonstrate how the model can be used to simulate the effects of prolonged fasting and intermittent fasting on selected metabolite concentrations and glucose flux. Furthermore, by simulating intermittent fasting the effect on the carbohydrate, the protein and the lipid storage is examined. We propose this method as a simple and intuitive approach for modeling the human metabolism, which is general, systematic and easy to incorporate. This could have potential applications in PK/PD drug development and in understanding metabolic disorders.

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arXiv2022

A whole-body multi-scale mathematical model for dynamic simulation of the metabolism in man

We propose a whole-body model of the metabolism in man as well as a generalized approach for modeling metabolic networks. Using this approach, we are able to write a large metabolic network in a systematic and compact way. We demonstrate the approach using a whole-body model of the metabolism of the three macronutrients, carbohydrates, proteins and lipids. The model contains 7 organs, 16 metabolites and 31 enzymatic reactions. All reaction rates are described by Michaelis-Menten kinetics with an addition of a hormonal regulator based on the two hormones insulin and glucagon. We incorporate ingestion of food in order to simulate metabolite concentrations during the feed-fast cycle. The model can simulate several days due to the inclusion of storage forms (glycogen, muscle protein and lipid droplets), that can be depleted if food is not ingested regularly. A physiological model incorporating complex cellular metabolism and whole-body mass dynamics can be used in virtual clinical trials. Such trials can be used to improve the development of medicine, treatment strategies such as control algorithms, and increase the likelihood of a successful clinical trial.

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