Nitrated fatty acids form membrane biochemical capacitors that restrain inflammation

Nitrated fatty acids (NO₂-FAs) are electrophilic lipid mediators that suppress inflammatory signaling, yet the sources, storage mechanisms, and physiological functions of endogenous NO₂-FAs remain poorly understood. Here, we identify nitro-conjugated linoleic acid (NO₂-CLA) as a diet-derived anti-inflammatory lipid that accumulates in membrane phospholipids and functions as a mobilizable biochemical reserve. Using cellular, murine, and human models, we show that phospholipids store NO₂-CLA under basal conditions and rapidly release it during inflammatory stress through phospholipase-dependent remodeling. Mobilized NO₂-CLA dampens cytokine production, limits inflammatory mediator formation, and preserves vascular homeostasis during endotoxemia. In both experimental inflammation and human sepsis, tissue and circulating pools of NO₂-CLA become depleted, indicating that consumption exceeds endogenous replenishment during acute inflammatory responses. These findings establish membrane phospholipids as reservoirs of endogenous NO₂-FAs and reveal a previously unrecognized mechanism by which diet, lipid metabolism, and redox signaling converge to regulate inflammation.