Bioactive Lipids

Bioactive lipids are a chemically heterogeneous group of lipids, which are recognized as key mediators of cell growth, adhesion, migration, signaling, and death and are present in every organ. The concept of bioactive lipids took off in the 1950s, but received its full recognition only in the past 20 years. Among the prominent roles exerted by bioactive lipids are immune regulation, inflammation and maintenance of homeostasis ^[1]. And they act predominantly via G-protein coupled receptors (e.g., the prostaglandin E receptor) or nuclear receptor binding (e.g., PPARG), but other signal transduction mechanisms have been described, such as the regulation of ion channel activity.

Classification

Bioactive lipids are divided by their biochemical functions into four major families: classical eicosanoids, endocannabinoids (eCBs), lysophospholipids/sphingolipids and specialized pro-resolving lipid mediators (SPMs) ^[1-2].

• Classical eicosanoids. Classical eicosanoids are a wide host of endogenous molecules, including more than 120 known compounds, which represents the most deeply characterized class of bioactive lipids as yet known. There are three classical types of eicosanoids: prostaglandins, thromboxanes, and leukotrienes and their main role is to amplify or reduce inflammation, coordinating leukocyte recruitment, cytokine and chemokine production, antibody formation, cell proliferation and migration, and antigen presentation.
• eCBs. eCBs include a group of bioactive lipids that are able (although with different affinities) to bind to and activate type-1 and type-2 cannabinoid receptors (CB1 and CB2). The two most well-characterized eCBs are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These molecules are ubiquitously produced by most tissues, and serve as a homeostatic system that controls several physiopathological states ultimately maintaining human health.
• Lysophospholipids and sphingolipids. Lysophospholipids and sphingolipids comprise several compounds with great molecular diversity (e.g., lysophosphatidic acid (LPA), sphingosylphosphorylcholine (SPC), sphingosines and ceramides) that regulate a rather wide range of cellular and physiological functions like membrane shaping, cell trafficking, cell growth and death, inflammatory cascades and leukocyte adhesion.
• SPMs. SPMs are a relatively novel family of endogenous lipids that are synthesized during acute inflammation either from v-6 AA or v-3 PUFAs like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) through the coordinated action of the macrophages, neutrophils, platelets and hypoxic endothelia. They can act as cues for counterbalance the inflammatory and also act as immunoresolvents to resolve the inflammation such as clearance of debris and of infective agents, analgesia and then gain of function.