How do lipids function as signaling molecules?

Lipid signaling involves diverse lipid classes with distinct pathways. Phosphoinositides: PI(3,4,5)P3 recruits Akt to membrane for activation (growth signaling); generated by PI3K, reversed by PTEN; critical in cancer. Sphingolipids: ceramide promotes apoptosis; sphingosine-1-phosphate promotes survival and migration. Eicosanoids: prostaglandins (cyclooxygenase products) modulate inflammation, pain, fever; leukotrienes (lipoxygenase products) in allergy and inflammation. DAG and IP3: from phospholipase C hydrolysis of PIP2; DAG activates PKC; IP3 releases ER calcium. Phosphatidic acid: from PLD activity, recruits kinases. Endocannabinoids: anandamide and 2-AG activate cannabinoid receptors. Analysis uses lipidomics mass spectrometry; perturbation uses specific inhibitors. Lipid signaling abnormalities underlie inflammatory diseases, cancer, and metabolic disorders.