Abstract
Elongation of very long-chain fatty acid (Elovl) proteins are key enzymes that catalyze the rate-limiting step in the fatty acid elongation pathway. The most recently discovered member of the Elovl family, Elovl8, has been proposed to be a fish-specific elongase with two gene paralogs described in teleosts. However, the biological functions of Elovl8 are still to be elucidated. In this study, we showed that in contrast to previous findings, elovl8 is not unique to teleosts, but displays a rather unique and ample phylogenetic distribution. For functional determination, we generated elovl8a (elovl8a−/−) and elovl8b (elovl8b−/−) zebrafish using CRISPR/Cas9 technology. Fatty acid composition in vivo and zebrafish liver cell experiments suggest that the substrate preference of Elovl8 overlapped with other existing Elovl enzymes. Zebrafish Elovl8a could elongate the polyunsaturated fatty acids (PUFAs) C18:2n-6 and C18:3n-3 to C20:2n-6 and C20:3n-3, respectively. Along with PUFA, zebrafish Elovl8b also showed the capacity to elongate C18:0 and C20:1. Gene expression quantification suggests that Elovl8a and Elovl8b may play a potentially important role in fatty acid biosynthesis. Overall, our results provide novel insights into the function of Elovl8a and Elovl8b, representing additional fatty acid elongases not previously described in chordates.
Highlights
Fatty acids (FAs) including saturated and unsaturated fatty acids have been shown to have significant roles in numerous critical biological processes and are major components of complex lipid molecules
While Elovl1, Elovl3, Elovl6, and Elovl7 are implicated in the elongation of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), members of the Elovl2, Elovl4, and Elovl5 groups are shown to participate in the elongation of polyunsaturated fatty acids (PUFAs) [4,5,6,7]
Within the Elovl8 clade, we observed that Teleostei species including D. rerio, present two elovl8 genes grouped into two clades elovl8a and elovl8b, which most probably resulted from the teleost specific genome duplication (TSGD) event
Summary
Fatty acids (FAs) including saturated and unsaturated fatty acids have been shown to have significant roles in numerous critical biological processes and are major components of complex lipid molecules. Upon the formation of palmitic acid (16:0), further modification involves the catalytic activities of fatty acid desaturase (Fads) and fatty acid elongases (Elovls) [1,2]. The latter extend the carbon chain of fatty acid through adding two carbon units at the carboxyl end in the endoplasmic reticulum, which has a rate-limiting effect in the process of fatty acid synthesis. The seven members of the Elovl family can be divided into two major groups on the basis of their substrate specificity. Elovl mainly elongates SFA and MUFA C20- and C22-acyl coenzyme A (CoA) [8]. The Elovl catalyzes the chain elongation of C16:0 to C18:0 and
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