Polyunsaturated fatty acid metabolism in a marine teleost, Nibe croaker Nibea mitsukurii: Functional characterization of Fads2 desaturase and Elovl5 and Elovl4 elongases

Kabeya, Naoki; Yamamoto, Yoji; Cummins, Scott F.; Elizur, Abigail; Yazawa, Ryosuke; Takeuchi, Yutaka; Haga, Yutaka; Satoh, Shuichi; Yoshizaki, Goro

doi:10.1016/j.cbpb.2015.06.005

Cited by 68 publications

(63 citation statements)

References 40 publications

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“…In the present study, we observed that the marine carnivore Nibe croaker N. mitsukurii possess a Fads2 that was the only non-Δ4 Fads2 studied that showed no detectable activity towards 24:5n−3. These results were consistent with the inability of N. mitsukurii Fads2 to desaturate 24:5n−3 to 24:6n−3 in yeast 25 and the accumulation of 24:5n−3, but not DHA, in transgenic N. mitsukurii carrying an elovl2 47 .…”

Section: Discussionsupporting

confidence: 85%

“…Studies using yeast as a heterologous expression system confirmed that the bifunctional ∆6∆5 Fads from zebrafish ( Danio rerio ) had ability to desaturate both C 18 and C 24 substrates at the ∆6 position 24 . However, the Nibe croaker ( Nibea mitsukurii ) ∆6 Fads catalysed the desaturation of C 18 but not C 24 substrates 25 . These findings suggested that the DHA biosynthetic capability varied among teleost fish and, interestingly, recent findings have demonstrated that, unlike other vertebrates, teleost fish have acquired alternative pathways for DHA biosynthesis during evolution 6 .…”

Section: Introductionmentioning

confidence: 99%

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Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Oboh

Kabeya

Carmona‐Antoñanzas

et al. 2017

Sci Rep

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109

108

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Docosahexaenoic acid (DHA) plays important physiological roles in vertebrates. Studies in rats and rainbow trout confirmed that DHA biosynthesis proceeds through the so-called “Sprecher pathway”, a biosynthetic process requiring a Δ6 desaturation of 24:5n−3 to 24:6n−3. Alternatively, some teleosts possess fatty acyl desaturases 2 (Fads2) that enable them to biosynthesis DHA through a more direct route termed the “Δ4 pathway”. In order to elucidate the prevalence of both pathways among teleosts, we investigated the Δ6 ability towards C24 substrates of Fads2 from fish with different evolutionary and ecological backgrounds. Subsequently, we retrieved public databases to identify Fads2 containing the YXXN domain responsible for the Δ4 desaturase function, and consequently enabling these species to operate the Δ4 pathway. We demonstrated that, with the exception of Δ4 desaturases, fish Fads2 have the ability to operate as Δ6 desaturases towards C24 PUFA enabling them to synthesise DHA through the Sprecher pathway. Nevertheless, the Δ4 pathway represents an alternative route in some teleosts and we identified the presence of putative Δ4 Fads2 in a further 11 species and confirmed the function as Δ4 desaturases of Fads2 from medaka and Nile tilapia. Our results demonstrated that two alternative pathways for DHA biosynthesis exist in teleosts.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Oboh

Kabeya

Carmona‐Antoñanzas

et al. 2017

Sci Rep

Self Cite

109

108

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“…Such an ability of Elovl4 has been noted as an important feature by which this enzyme can contribute to DHA biosynthesis through the Sprecher pathway in species that, like most marine farmed species including the large yellow croaker, might have lost Elovl2. Thus, the elongation product of Elovl4, namely 24:5n-3, can be desaturated to 24:6n-3 and subsequently chain shortened to 22:6n-3 by partial β-oxidation 36 Similar activities were also demonstrated for Elovl4 from zebrafish (isoform b), Atlantic salmon, cobia, rabbitfish, nibe croaker and orange-spotted grouper 15, 25, 31, 32, 37, 38 .…”

Section: Discussionmentioning

confidence: 60%

Functional characterization and differential nutritional regulation of putative Elovl5 and Elovl4 elongases in large yellow croaker (Larimichthys crocea)

Monroig

Wang

et al. 2017

Sci Rep

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In the present study, two elongases, Elovl4 and Elovl5, were functionally characterized and their transcriptional regulation in response to n-3 LC-PUFA administration were investigated in vivo and in vitro. We previously described the molecular characterization of croaker elovl5. Here, we report the full-length cDNA sequence of croaker elovl4, which contained 1794 bp (excluding the polyA tail), including 909 bp of coding region that encoded a polypeptide of 302 amino acids possessing all the characteristic features of Elovl proteins. Functional studies showed that croaker Elovl5, displayed high elongation activity towards C18 and C20 PUFA, with only low activity towards C22 PUFA. In contrast, croaker Elovl4 could effectively convert both C20 and C22 PUFA to longer polyenoic products up to C34. n-3 LC-PUFA suppressed transcription of the two elongase genes, as well as srebp-1 and lxrα, major regulators of hepatic lipid metabolism. The results of dual-luciferase reporter assays and in vitro studies both indicated that the transcriptions of elovl5 and elovl4 elongases could be regulated by Lxrα. Moreover, Lxrα could mediate the transcription of elovl4 directly or indirectly through regulating the transcription of srebp-1. The above findings contribute further insight and understanding of the mechanisms regulating LC-PUFA biosynthesis in marine fish species.

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“…Interestingly, both D. rerio Elovl4 showed an ability to elongate saturated fatty acids, but only Elovl4b appeared to have a role in the biosynthesis of very long-chain (>C 24 ) polyunsaturated fatty acids (VLC-PUFA) [6]. Since this pioneer study in fish, further elovl4 cDNA sequences have been studied in a variety of species including Atlantic salmon, Nibe croaker, orange-spotted grouper and rabbitfish [8][9][10][11]. Interestingly, with the exception of the zebrafish elovl4a [6], all elovl4 cDNA cloned from other teleost fish species have been confirmed to be orthologues of the zebrafish elovl4b, although in silico searches indicated that virtually all teleosts possess at least one copy of both elovl4a and elovl4b [4].…”

Section: Introductionmentioning

confidence: 99%

Elongation of very Long‐Chain (>C₂₄) Fatty Acids in Clarias gariepinus: Cloning, Functional Characterization and Tissue Expression of elovl4 Elongases

Oboh

Navarro

Tocher

et al. 2017

Lipids

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Elongation of very long-chain fatty acid 4 (Elovl4) proteins participate in the biosynthesis of very long-chain (>C24) saturated and polyunsaturated fatty acids (FA). Previous studies have shown that fish possess two different forms of Elovl4, termed Elovl4a and Elovl4b. The present study aimed to characterize both molecularly and functionally two elovl4 cDNA from the African catfish Clarias gariepinus. The results confirmed that C. gariepinus possessed two elovl4-like elongases with high homology to two previously characterized Elovl4 from Danio rerio, and thus they were termed accordingly as Elovl4a and Elovl4b. The C. gariepinus Elovl4a and Elovl4b have open reading frames (ORF) of 945 and 915 base pairs, respectively, encoding putative proteins of 314 and 304 amino acids, respectively. Functional characterization in yeast showed both Elovl4 enzymes have activity towards all the PUFA substrates assayed (18:4n-3, 18:3n-6, 20:5n-3, 20:4n-6, 22:5n-3, 22:4n-6 and 22:6n-3), producing elongated products of up to C36. Moreover, the C. gariepinus Elovl4a and Elovl4b were able to elongate very long-chain saturated FA (VLC-SFA) as denoted by increased levels of 28:0 and longer FA in yeast transformed with elovl4 ORF compared to control yeast. These results confirmed that C. gariepinus Elovl4 play important roles in the biosynthesis of very long-chain FA. Tissue distribution analysis of elovl4 mRNAs showed both genes were widely expressed in all tissues analyzed, with high expression of elovl4a in pituitary and brain, whereas female gonad and pituitary had the highest expression levels for elovl4b.

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Polyunsaturated fatty acid metabolism in a marine teleost, Nibe croaker Nibea mitsukurii: Functional characterization of Fads2 desaturase and Elovl5 and Elovl4 elongases

Cited by 68 publications

References 40 publications

Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Functional characterization and differential nutritional regulation of putative Elovl5 and Elovl4 elongases in large yellow croaker (Larimichthys crocea)

Elongation of very Long‐Chain (>C₂₄) Fatty Acids in Clarias gariepinus: Cloning, Functional Characterization and Tissue Expression of elovl4 Elongases

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Polyunsaturated fatty acid metabolism in a marine teleost, Nibe croaker Nibea mitsukurii: Functional characterization of Fads2 desaturase and Elovl5 and Elovl4 elongases

Cited by 68 publications

References 40 publications

Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Two alternative pathways for docosahexaenoic acid (DHA, 22:6n-3) biosynthesis are widespread among teleost fish

Functional characterization and differential nutritional regulation of putative Elovl5 and Elovl4 elongases in large yellow croaker (Larimichthys crocea)

Elongation of very Long‐Chain (>C24) Fatty Acids in Clarias gariepinus: Cloning, Functional Characterization and Tissue Expression of elovl4 Elongases

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Elongation of very Long‐Chain (>C₂₄) Fatty Acids in Clarias gariepinus: Cloning, Functional Characterization and Tissue Expression of elovl4 Elongases