DOI: 10.3390/lipidology3020020 ISSN: 2813-7086

Lipid-Regulated State Transitions in Inflammation, Regeneration, and Chronic Disease

Ola A. Al-Ewaidat, Moawiah M. Naffaa

Lipids are commonly viewed as membrane components, energy sources, or precursors of signaling molecules, yet accumulating evidence indicates a broader role in determining the functional state of cells. In this review, we present an integrative cross-domain synthesis in which lipids are discussed as important modulators of cellular functional state across inflammation, tissue regeneration, and chronic disease. We discuss how membrane lipid composition shapes receptor and ion-channel signaling, how bioactive lipid mediators govern the balance between inflammatory initiation and resolution, and how lipid metabolism regulates stem-cell quiescence, activation, and regenerative capacity. We integrate these mechanisms to show how disruption of lipid-regulated processes may bias tissues toward persistent inflammation, impaired repair, and disease progression in conditions such as rheumatic disorders, fibrosis, and neurodegeneration. Depending on context, such lipid alterations may function as causal contributors, permissive conditions, or downstream signatures of pathological state transitions. Finally, we consider how pharmacological and nutritional modulation of lipid pathways may influence cellular states, while emphasizing that the main contribution of this review is a conceptual state-transition framework that links membrane architecture, mediator balance, and lipid metabolic flux across inflammation, regeneration, and chronic disease.

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