Liu_2025_Injury_56_112892

Fat embolism syndrome (FES) is a severe complication of orthopedic trauma and surgery, associated with high mortality. Traditional mechanical obstruction and biochemical lipotoxicity models explain only part of its pathogenesis and cannot account for the sustained progression, multi-organ involvement, and irreversibility of FES. We propose a novel concept of Lipid Pathological Resonance (LPR)-a self-reinforcing loop involving triglyceride (TG) extravasation, hydrolysis into free fatty acids (FFA), hypoxic signaling, and inflammatory amplification. This model integrates lipid metabolic imbalance, immune activation, and structural injury into a unified kinetic framework, clearly distinguishing it from the classical lipotoxicity theory. Drawing upon multi-omics, pathological, and clinical evidence, we highlight the central role of LPR in the pathogenesis of FES and explore potential therapeutic strategies, including lipase modulation, vascular barrier protection, and inflammation control.