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Related Experiment Video

Updated: Jan 17, 2026

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Resolving versus non-resolving sphingolipid dynamics during macrophage activation: a time-resolved metabolic

Nathan F Chiappa1, Nidhi Lal1, Edward A Botchwey2

  • 1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.

Journal of Lipid Research
|September 17, 2025
PubMed
Summary

Sphingolipid metabolism in macrophages shifts during inflammation, creating distinct cell states. Targeting specific metabolic pathways may help resolve inflammation and prevent disease.

Keywords:
ceramidesinflammationlipidomicssphingolipidssphingosine phosphate

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Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Systems Biology

Background:

  • Sphingolipids regulate inflammation and cell fate, with key metabolites like ceramide and sphingosine 1-phosphate having opposing roles.
  • Macrophage sphingolipid balance is crucial for host defense, pathogenesis, and wound healing.

Purpose of the Study:

  • To develop a time-resolved model of sphingolipid metabolism in RAW 264.7 macrophages during inflammation.
  • To systematically map dynamic changes in the sphingolipid network and identify key regulatory nodes.

Main Methods:

  • Integrated measured metabolite concentrations with dynamic flux estimation and enzyme kinetics.
  • Developed a computational systems-level analysis approach.
  • Stimulated RAW 264.7 macrophages with KdO2-Lipid A to model inflammatory response.

Main Results:

  • Revealed a three-phase pattern of sphingolipid remodeling correlating with distinct macrophage functional states.
  • Classified metabolites into 'resolving' and 'non-resolving' lipids based on their return to basal levels.
  • Identified potential drug targets for modulating sphingolipid homeostasis and inflammation resolution.

Conclusions:

  • Targeted modulation of specific sphingolipid metabolic nodes can influence inflammation resolution.
  • Computational systems-level analysis is valuable for understanding sphingolipid dynamics in macrophages.
  • Findings may guide therapeutic strategies for inflammatory diseases by preventing pathological amplification of signals.