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

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. Exogenous addition of iso‐C16:0 reprogrammed macrophage energy metabolism by upregulating the FABP4/PPAR‐γ pathway, enhancing FAO, TCA cycle, and OXPHOS, while inhibiting glycolytic pathway flux. This greatly inhibits LPS/IFN‐γ‐induced M1 proinflammatory macrophages and increases the proportion of M2 antiinflammatory macrophages.