{"title":"A mathematical model of microglia glucose metabolism and lactylation with positive feedback","authors":"Kamila Larripa , Anca Rǎdulescu","doi":"10.1016/j.jtbi.2025.112049","DOIUrl":null,"url":null,"abstract":"<div><div>In this paper, we present and analyze a model for metabolism and lactylation in a single microglia. The model includes positive feedback from lactylation in the glycolytic pathway, and links metabolism and inflammation. Specific pathways include the transition of glucose to pyruvate to lactate in a microglia, as well as the gradient transport of glucose and lactate into and out of the cell. Additionally, the upregulation of certain pathways by either epigenetic modification or the inflammatory response are included. Bifurcation and sensitivity analyses demonstrate the importance of key parameters and pathways in the model, specifically the role of lactylation. Our model is validated by qualitatively reproducing recent in vitro experiments in which exogenous glucose and lactate are modified.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"602 ","pages":"Article 112049"},"PeriodicalIF":2.0000,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Theoretical Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022519325000153","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
In this paper, we present and analyze a model for metabolism and lactylation in a single microglia. The model includes positive feedback from lactylation in the glycolytic pathway, and links metabolism and inflammation. Specific pathways include the transition of glucose to pyruvate to lactate in a microglia, as well as the gradient transport of glucose and lactate into and out of the cell. Additionally, the upregulation of certain pathways by either epigenetic modification or the inflammatory response are included. Bifurcation and sensitivity analyses demonstrate the importance of key parameters and pathways in the model, specifically the role of lactylation. Our model is validated by qualitatively reproducing recent in vitro experiments in which exogenous glucose and lactate are modified.
期刊介绍：
The Journal of Theoretical Biology is the leading forum for theoretical perspectives that give insight into biological processes. It covers a very wide range of topics and is of interest to biologists in many areas of research, including:
• Brain and Neuroscience
• Cancer Growth and Treatment
• Cell Biology
• Developmental Biology
• Ecology
• Evolution
• Immunology,
• Infectious and non-infectious Diseases,
• Mathematical, Computational, Biophysical and Statistical Modeling
• Microbiology, Molecular Biology, and Biochemistry
• Networks and Complex Systems
• Physiology
• Pharmacodynamics
• Animal Behavior and Game Theory
Acceptable papers are those that bear significant importance on the biology per se being presented, and not on the mathematical analysis. Papers that include some data or experimental material bearing on theory will be considered, including those that contain comparative study, statistical data analysis, mathematical proof, computer simulations, experiments, field observations, or even philosophical arguments, which are all methods to support or reject theoretical ideas. However, there should be a concerted effort to make papers intelligible to biologists in the chosen field.
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