Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

Abstract

This article is available online at http://www.jlr.org tively rare compared with the abundance of FA containing 16-22 carbons, they are widely distributed in higher plants and animals ( 1-10 ). They are found in most living organisms from humans to autotrophic and heterotrophic lower organisms, including microalgae, sponges, bacteria, and fungi ( 1,9,(11)(12)(13)(14)(15). VLC-FA are found mainly in seed oils, plant waxes, cutin, suberin, skin, hair, and wax glands ( 1 ), whereas VLC-PUFA are found primarily in retina, brain ( 1, 16 ), testis, and spermatozoa ( 17-19 ).The unusually long hydrocarbon chains with 3 -9 double bonds, which are prone to oxidative damage, combined with the small quantities found in mammalian tissues, have made them diffi cult to isolate and analyze in detail over the years ( 9 ). Very little is therefore known about the metabolism and function of VLC-PUFA and VLC-FA in mammals, except for their increase in disorders of peroxisomal function ( 3,16,20,21 ), as components of the secretions of meibomian glands (22)(23)(24)(25)(26)(27), and their reduction in animal models of autosomal dominant Stargardt-like macular dystrophy (STGD3) ( 28-32 ), a juvenile form of macular degeneration. In contrast, the roles of long-chain PUFA (LC-PUFA) with carbon chains that range from C18 to C24 are fairly well understood, especially in the retina and other neural tissues. A detailed account on the role and function of LC-PUFA in the retina was reviewed earlier (33)(34)(35)(36).Recent interest in the molecular and physiological roles of VLC-PUFA in the retina came from the fi nding that the gene associated with STGD3 shared sequence homologies with genes involved in FA elongation ( 37,38 ) Abbreviations: AOX, acyl-CoA oxidase; DHA or 22:6n3, docosahexaenoic acid; ELOVL, elongation of very long-chain FA; ELOVL4, elongation of very long-chain FA-4; ERG, electroretinogram; LC-PUFA, long-chain PUFA; PC, phosphatidylcholine; ROS, retinal outer segments; RPE, retinal pigment epithelium; STGD1, recessive Stargardt degeneration; STGD3, autosomal dominant Stargardt-like macular dystrophy; VLC-FA, very long-chain saturated or monounsaturated FA; VLC-PUFA, very long-chain PUFA.

Serum levels of lipid metabolites in age‐related macular degeneration

“…Our studies recapitulated the results obtained in patients with AMD (61,62), further denoting the complexity of the macular degeneration phenotypes. However, very-long-chain polyunsaturated fatty acids (whose production is catalyzed by ELOVL-4) are similar to DHA because of their role in photoreceptor function and integrity (63). As a consequence, it is reasonable to expect that, analogous to DHA, changes in levels of the very long polyunsaturated fatty acids could be early indicators of declining photoreceptor health.…”

Biosynthesis of very long-chain fatty acids (C>24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase

“…Their relative low abundance compared to shorter chain FA (≤ C24) and the difficulty of their analysis has hindered investigation of the functions and metabolism of VLC-FA. Recent advances in analytical technology will enable more accurate characterisation of VLC-FA that will likely accelerate the understanding of the functions that these compounds play in living organisms (Agbaga et al, 2010b).…”

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

“…This pathway is believed to mainly occur within the liver [59], but there is some evidence that brain, retina and testis also have high expression of the genes encoding the relevant enzymes compared with other tissues [60,61]. Competition exists between the conversion of ω-6 and ω-3 fatty acids as both utilise this same metabolic pathway.…”