RT info:eu-repo/semantics/article
T1 Phosphatidylcholine-bound palmitoleic acid: A bioactive key to unlocking macrophage anti-inflammatory functions
A1 Bermúdez Arias, Miguel Ángel
A1 Meana González, Clara
A1 Garrido Jiménez, Álvaro
A1 Pérez Encabo, Alfonso
A1 Balboa, María A.
A1 Balsinde, Jesús
AB Inflammatory processes are central to the progression of numerous chronic conditions, including cardiovascular and metabolic disorders, with macrophages playing a pivotal role in these responses. Monounsaturated fatty acids, including palmitoleic acid (16:1 n − 7), have been implicated in modulating inflammation, yet their precise molecular mechanisms of action remain incompletely understood. Notably, in macrophages, 16:1 n − 7 is preferentially esterified into a specific phosphatidylcholine (PC) species, PC(16:0/16:1 n − 7), raising the possibility that its biological activity is governed by this lipid-bound form. Here, we demonstrate that the anti-inflammatory effects of 16:1 n − 7 in macrophages are mediated through its incorporation into this PC species. Using synthetic phospholipids and multiple activation stimuli, we show that PC(16:0/16:1 n − 7) directly regulates macrophage activation. It suppresses NF-κB signaling, reprograms gene expression, and promotes a shift toward an anti-inflammatory, M2-like phenotype that enhances phagocytic capacity. These effects are preserved in ether analogs resistant to phospholipase-mediated hydrolysis, confirming that the release of free 16:1 n − 7 is not required. These findings reveal a previously unrecognized lipid-driven mechanism of immunomodulation, in which specific structural features of PC(16:0/16:1 n − 7) confer intrinsic bioactivity. Our study broadens understanding of immunometabolic regulation by membrane phospholipids, and provides a mechanistic basis for the pharmacotherapeutic potential of defined lipid species in reprogramming macrophage function in inflammatory diseases.
SN 0753-3322
YR 2025
FD 2025
LK https://uvadoc.uva.es/handle/10324/79599
UL https://uvadoc.uva.es/handle/10324/79599
LA spa
NO Biomedicine & Pharmacotherapy, Oct 2025, vol. 192, p. 118652
NO Producción Científica
DS UVaDOC
RD 09-ene-2026