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.