A mathematical model of microglia glucose metabolism and lactylation with positive feedback.

J Theor Biol

Department of Mathematics, SUNY New Paltz, 1 Hawk Drive, New Paltz, 12561, NY, United States. Electronic address:

Published: April 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article 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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtbi.2025.112049DOI Listing

Publication Analysis

Top Keywords

metabolism lactylation
8
positive feedback
8
glucose lactate
8
mathematical model
4
model microglia
4
glucose
4
microglia glucose
4
glucose metabolism
4
lactylation
4
lactylation positive
4

Similar Publications

Lactylation as a metabolic-epigenetic nexus in epilepsy: Mechanisms and therapeutic implications.

Neurobiol Dis

September 2025

Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000, Guizhou, PR China; Key Laboratory of Brain Function and Brain Disease Prevention and Treatment of Guizhou Province, Zunyi 563000, Guizhou, PR China; The Collaborative Innovation Center of Tis

Lactylation is a novel post-translational modification (PTM) mediated by lactate, which dynamically regulates protein functions and gene expression by covalently attaching lactate groups to lysine residues. Recent studies have shown that abnormal lactate metabolism not only contributes to the pathogenesis of epilepsy through microenvironment acidification but also influences neuroinflammation, energy metabolism imbalance, neurotransmitter dysregulation, synaptic plasticity, and epigenetic regulation via lactylation. This positions lactylation as a critical metabolic-epigenetic intersection in the pathological mechanisms of epilepsy.

View Article and Find Full Text PDF

Introduction: Lactate has emerged as a multifunctional signaling molecule regulating various physiological and pathological processes. Furthermore, lactylation, a newly identified posttranslational modification triggered by lactate accumulation, plays significant roles in human health and diseases. This study aims to investigate the roles of lactate/lactylation in respiratory diseases.

View Article and Find Full Text PDF

Post-translational modifications (PTMs) are chemical modifications that occur on specific amino acid residues after protein biosynthesis, which can affect protein function by altering protein structure, localization and activity, thus expanding protein diversity. Extensive research has demonstrated that PTMs can regulate various metabolic processes, such as glucose and lipid metabolism, as well as immune modulation in tumor cells, thereby promoting tumor initiation, progression, and metastasis. In this article, we systematically review a class of emerging PTMs whose roles in tumor metabolism and immune regulation have gradually been recognized in recent years, including six types: lactylation, palmitoylation, SUMOylation, succinylation, crotonylation, and myristoylation.

View Article and Find Full Text PDF

Background: Emerging evidence indicates that lactase-mediated histone lactylation can activate osteogenic gene expression and promote bone formation. However, the role of lactylation-related genes (LRGs) in osteoporosis (OP) remains unclear. This study aims to clarify the key roles of LRGs and the molecular mechanisms of related biomarkers in OP.

View Article and Find Full Text PDF

Thyroid carcinoma is among the most common endocrine system malignancies. Lactate metabolism and lactylation modification roles in carcinogenesis and development have garnered more interest in recent years. The expression and function of lactate transporters (MCTs) and significant metabolic enzymes are included in our summary of the characterisation of lactate metabolism in thyroid cancer.

View Article and Find Full Text PDF