PUFA-derived endocannabinoids: an overview.

Following on from the discovery of cannabinoid receptors, of their endogenous agonists (endocannabinoids) and of the biosynthetic and metabolic enzymes of the endocannabinoids, significant progress has been made towards the understanding of the role of the endocannabinoid system in both physiological and pathological conditions. Endocannabinoids are mainly n-6 long-chain PUFA (LCPUFA) derivatives that are synthesised by neuronal cells and inactivated via a two-step process that begins with their transport from the extracellular to the intracellular space and culminates in their intracellular degradation by hydrolysis or oxidation. Although the enzymes responsible for the biosynthesis and metabolism of endocannabinoids have been well characterised, the processes involved in their cellular uptake are still a subject of debate. Moreover, little is yet known about the roles of endocannabinoids derived from n-3 LCPUFA such as EPA and DHA. Here, I provide an overview of what is currently known about the mechanisms for the biosynthesis and inactivation of endocannabinoids, together with a brief analysis of the involvement of the endocannabinoids in both food intake and obesity. Owing to limited space, recent reviews will be often cited instead of original papers.