A unified framework for prediction of liver steatosis dynamics in response to different diet and drug interventions.

Autor: Simonsson C; Department of Biomedical Engineering, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Radiation Physics, Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden., Nyman E; Department of Biomedical Engineering, Linköping University, Linköping, Sweden., Gennemark P; Department of Biomedical Engineering, Linköping University, Linköping, Sweden; Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Gustafsson P; Department of Biomedical Engineering, Linköping University, Linköping, Sweden; Department of Media and Information Technology, Linköping University, Norrköping, Sweden., Hotz I; Department of Media and Information Technology, Linköping University, Norrköping, Sweden., Ekstedt M; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Gastroenterology and Hepatology, Department of Health, Medicine and Caring Sciences, Linköping University, Sweden., Lundberg P; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden; Department of Radiation Physics, Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden., Cedersund G; Department of Biomedical Engineering, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden. Electronic address: gunnar.cedersund@liu.se.
Jazyk: angličtina
Zdroj: Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2024 Jun; Vol. 43 (6), pp. 1532-1543. Date of Electronic Publication: 2024 May 09.
DOI: 10.1016/j.clnu.2024.05.017
Abstrakt: Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder, characterized by the accumulation of excess fat in the liver, and is a driving factor for various severe liver diseases. These multi-factorial and multi-timescale changes are observed in different clinical studies, but these studies have not been integrated into a unified framework. In this study, we aim to present such a unified framework in the form of a dynamic mathematical model.
Methods: For model training and validation, we collected data for dietary or drug-induced interventions aimed at reducing or increasing liver fat. The model was formulated using ordinary differential equations (ODEs) and the mathematical analysis, model simulation, model formulation and the model parameter estimation were all performed in MATLAB.
Results: Our mathematical model describes accumulation of fat in the liver and predicts changes in lipid fluxes induced by both dietary and drug interventions. The model is validated using data from a wide range of drug and dietary intervention studies and can predict both short-term (days) and long-term (weeks) changes in liver fat. Importantly, the model computes the contribution of each individual lipid flux to the total liver fat dynamics. Furthermore, the model can be combined with an established bodyweight model, to simulate even longer scenarios (years), also including the effects of insulin resistance and body weight. To help prepare for corresponding eHealth applications, we also present a way to visualize the simulated changes, using dynamically changing lipid droplets, seen in images of liver biopsies.
Conclusion: In conclusion, we believe that the minimal model presented herein might be a useful tool for future applications, and to further integrate and understand data regarding changes in dietary and drug induced changes in ectopic TAG in the liver. With further development and validation, the minimal model could be used as a disease progression model for steatosis.
Competing Interests: Conflict of interest Gunnar Cedersund is the owner of SUND sound medical decisions AB (unrelated to the work presented herein). Peter Gennemark is an employee of AstraZeneca and holds stock/stock options (unrelated to the work presented herein).
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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