ArticleFrontiers in pharmacology2022
A Quantitative Systems Pharmacology Model of Liver Lipid Metabolism for Investigation of Non-Alcoholic Fatty Liver Disease.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 8 citations in OpenAlex.
- A Step-by-Step Workflow for Performing In Silico Clinical Trials With Nonlinear Mixed Effects Models.CPT: pharmacometrics & systems pharmacology · 2025Article
- Impact of Dapagliflozin on Hepatic Lipid Metabolism and a Dynamic Model of Ketone Body Levels.The AAPS journal · 2025Article
- A Quantitative Systems Pharmacology Model of Liver Lipid Metabolism for Investigation of Non-Alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2022Article
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3 authors at 1 institution in 1 country.
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Abstract
Non-alcoholic fatty liver disease is a metabolic and inflammatory disease that afflicts many people worldwide and presently has few treatment options. To enhance the preclinical to clinical translation and the design of early clinical trials for novel therapeutics, we developed a Quantitative Systems Pharmacology model of human hepatocyte lipid metabolism. The intended application of the model is for simulating anti-steatotic therapies for reversing fatty liver. We parameterized the model using literature data from humans with both normal and elevated liver fat. We assessed that the model construct was sufficient to generate a virtual population of NAFLD patients that matched relevant statistics of a published clinical cohort, and then validated the model response to treatment by simulating pioglitazone and diet intervention in the virtual population. Finally, a sensitivity analysis was performed to determine the best points of intervention for reducing hepatic steatosis. Analysis of the model suggests the most potent method for reducing hepatic steatosis is by limiting non-esterified fatty acid flux from the adipose to the liver.
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