lipidsignaler

Lipid signals, or lipid mediators, are bioactive lipids produced on demand from membrane phospholipids or sphingolipids. They act locally in autocrine or paracrine fashion and typically have short lifespans, enabling rapid and time-controlled responses. Lipid signaling coordinates processes such as inflammation, immunity, vascular tone, coagulation, metabolism, and tissue repair.

The main classes of lipid mediators include eicosanoids (prostaglandins, thromboxanes, leukotrienes, and lipoxins) derived from arachidonic acid via cyclooxygenases, lipoxygenases, and cytochrome P450 pathways; platelet-activating factor; endocannabinoids; and lysophospholipids such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), as well as other sphingolipid metabolites like ceramide-1-phosphate. Their production relies on phospholipases that release fatty acids from membranes and on specific enzymes that generate active mediators from these fatty acids.

Receptors for lipid mediators are diverse, with many acting through G protein-coupled receptors (GPCRs), including prostaglandin and leukotriene receptors, as well as LPA and S1P receptors. Some lipid mediators interact with nuclear receptors such as peroxisome proliferator-activated receptors (PPARs), linking lipid signaling to gene expression. Termination of signaling occurs through enzymatic inactivation, reuptake, or degradation by specific hydrolases.

In physiology and medicine, lipid signals regulate pain, fever, inflammation, vascular permeability, bronchoconstriction, and metabolic homeostasis. Dysregulation is implicated in asthma, cardiovascular disease, metabolic disorders, neuroinflammation, and cancer. Therapeutic approaches target specific mediators or their receptors, exemplified by NSAIDs that inhibit cyclooxygenases and leukotriene antagonists used in asthma, or by PPAR-targeted drugs for metabolic diseases.