Fig. 1.

Outline of ELOVL5 activities in health and disease. a Schematic representation of PUFA biosynthetic pathways highlighting the role of ELOVL5 in converting C18 and C20 PUFA substrates in both n-3 and n-6 lineages. ALA, α-linolenic acid; LA, linoleic acid; ETA, eicosatetraenoic acid; EPA, eicosapentaenoic acid; DGLA, dihomo-γ-linolenic acid; and AA, arachidonic acid. PUFAs generated in these pathways are incorporated into structural lipids (membrane components) and functional lipids (bioactive mediators). b ELOVL5 also elongates substrates of the n-7 and n-9 series in non-physiological conditions such as: (i) essential fatty acid deficiency, where ELOVL5 had been reported to elongate C18:1n-9 to mead acid (C20:3n-9), which acts by replacing the missing PUFAs in membrane biosynthesis (Hayashi et al. 2020); (ii) in prostate cancer, ELOVL5 synthesizes the monounsaturated fatty acid cis-vaccenic acid (C18:1), which serves to maintain redox homeostasis (Centenera et al. 2021); in diet-induced obesity, murine Elovl5 regulates gluconeogenesis through the mTORC2-Akt-FOXO1 pathway (Hwang et al. 2018). c A multiple sequence alignment of human ELOVL1-7 was generated using the MAFFT alignment program, and used to produce a neighbour-joining phylogenetic tree illustrating the relationship between the human ELOVLs. The aa similarity matrix, generated using the SIAS (Sequences Identities and Similarities) program, showed the % aa sequence identity of the other human ELOVLs with respect to human ELOVL5