Monomethyl Branched-Chain Fatty Acids Suppress M1 Macrophage Polarization via FABP4/PPAR-γ Signaling Pathway

Mol Nutr Food Res. 2024 Oct;68(20):e2400310. doi: 10.1002/mnfr.202400310. Epub 2024 Sep 24.

Abstract

Scope: Monomethyl-branched chain fatty acids (mmBCFAs) are found in a variety of food sources and are of great interest due to their potent antiinflammatory properties. However, most of the current researches have concentrated on the relationship between mmBCFAs and intestinal inflammation, and there is a large gap in the biological mechanisms involved behind their antiinflammatory effects.

Methods and results: The present study examines the role of mmBCFAs in modulating macrophage polarization. The results demonstrate that iso-C16:0 significantly inhibits macrophages M1 proinflammatory polarization through regulating FABP4/PPAR-γ pathway. Proteomics and molecular biology experiments verify that metabolic reprogramming is involved in the inhibition of M1 macrophage, referring to the upregulation of fatty acid oxidation, TCA cycle, and oxidative phosphorylation, as well as downregulation of glycolytic flux.

Conclusion: In summary, this study offers a novel perspective on the antiinflammatory effects mediated by mmBCFAs.

Keywords: PPAR‐γ signaling pathway; inflammation; macrophage polarization; metabolic reprogramming; monomethyl branched‐chain fatty acids.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Fatty Acid-Binding Proteins* / metabolism
  • Fatty Acids* / metabolism
  • Fatty Acids* / pharmacology
  • Macrophages* / drug effects
  • Macrophages* / metabolism
  • Mice
  • PPAR gamma* / metabolism
  • RAW 264.7 Cells
  • Signal Transduction* / drug effects

Substances

  • PPAR gamma
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Fabp4 protein, mouse
  • Anti-Inflammatory Agents