Supplies of marine fish oils (FO) are limited and continued growth in aquaculture production dictates that substitutes must be found that do not compromise fish health and product quality. In this study the suitability of crude palm oil (PO) as a replacement for FO in diets of Atlantic salmon was investigated. Duplicate groups of Atlantic salmon post-smolts were fed four practical-type diets in which the added lipid was either 100% FO and 0% crude PO (0% PO); 75% FO and 25% PO (25% PO); 50% FO and 50% PO (50% PO); and 100% PO, for 30 wk. There were no effects of diet on growth rate or feed conversion ratio nor were any histopathological lesions found in liver, heart or muscle. Lipid deposition was greatest in fish fed 0% PO and was significantly greater than in fish fed 50% and 100% PO. Fatty acid compositions of muscle total lipid were correlated with dietary PO inclusion such that the concentrations of 16:0, 18:1(n-9), 18:2(n-6), total saturated fatty acids and total monoenoic fatty acids increased linearly with increasing dietary PO. The concentration of eicosapentaenoic acid [20:5(n-3)] was reduced significantly with increasing levels of dietary PO but the concentration of docosahexaenoic acid [22:6(n-3)] was significantly reduced only in fish fed 100% PO, compared with the other three treatments. Similar diet-induced changes were seen in liver total lipid fatty acid compositions. Hepatic fatty acid desaturation and elongation activities were approximately 10-fold greater in fish fed 100% PO than in those fed 0% PO. This study suggests that PO can be used successfully as a substitute for FO in the culture of Atlantic salmon in sea water. However, at levels of PO inclusion above 50% of dietary lipid, significant reductions in muscle 20:5(n-3), 22:6(n-3) and the (n-3):(n-6) PUFA ratio occur, resulting in reduced availability of these essential (n-3) highly unsaturated fatty acids to the consumer.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in which motoneurons of the spinal cord and motor cortex die, resulting in progressive paralysis. This condition has no cure and results in eventual death, usually within 1-5 years of diagnosis. Although the specific etiology of ALS is unknown, 20% of familial cases of the disease carry mutations in the gene encoding Cu/Zn superoxide dismutase-1 (SOD1). Transgenic mice overexpressing human mutant SOD1 have a phenotype and pathology that are very similar to that seen in human ALS patients. Here we show that treatment with arimoclomol, a coinducer of heat shock proteins (HSPs), significantly delays disease progression in mice expressing a SOD1 mutant in which glycine is substituted with alanine at position 93 (SOD1(G93A)). Arimoclomol-treated SOD1(G93A) mice show marked improvement in hind limb muscle function and motoneuron survival in the later stages of the disease, resulting in a 22% increase in lifespan. Pharmacological activation of the heat shock response may therefore be a successful therapeutic approach to treating ALS, and possibly other neurodegenerative diseases.

As the global population and its demand for seafood increases more of our fish will come from aquaculture. Farmed Atlantic salmon are a global commodity and, as an oily fish, contain a rich source of the health promoting long-chain omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Replacing the traditional finite marine ingredients, fishmeal and fish oil, in farmed salmon diets with sustainable alternatives of terrestrial origin, devoid of EPA and DHA, presents a significant challenge for the aquaculture industry. By comparing the fatty acid composition of over 3,000 Scottish Atlantic salmon farmed between 2006 and 2015, we find that terrestrial fatty acids have significantly increased alongside a decrease in EPA and DHA levels. Consequently, the nutritional value of the final product is compromised requiring double portion sizes, as compared to 2006, in order to satisfy recommended EPA + DHA intake levels endorsed by health advisory organisations. Nevertheless, farmed Scottish salmon still delivers more EPA + DHA than most other fish species and all terrestrial livestock. Our findings highlight the global shortfall of EPA and DHA and the implications this has for the human consumer and examines the potential of microalgae and genetically modified crops as future sources of these important fatty acids.

⌬5 and ⌬6 fatty acid desaturases are critical enzymes in the pathways for the biosynthesis of the polyunsaturated fatty acids arachidonic, eicosapentaenoic, and docosahexaenoic acids. They are encoded by distinct genes in mammals and Caenorhabditis elegans. This paper describes a cDNA isolated from zebrafish (Danio rerio) with high similarity to mammalian ⌬6 desaturase genes. The 1,590-bp sequence specifies a protein that, in common with other fatty acid desaturases, contains an N-terminal cytochrome b5 domain and three histidine boxes, believed to be involved in catalysis. When the zebrafish cDNA was expressed in Saccharomyces cerevisiae it conferred the ability to convert linoleic acid (18:2n-6) and ␣-linolenic acid (18:3n-3) to their corresponding ⌬6 desaturated products, 18:3n-6 and 18:4n-3. However, in addition it conferred on the yeast the ability to convert di-homo-␥-linoleic acid (20:3n-6) and eicosatetraenoic acid (20:4n-3) to arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), respectively, indicating that the zebrafish gene encodes an enzyme having both ⌬5 and ⌬6 desaturase activity. The zebrafish ⌬5͞⌬6 desaturase may represent a component of a prototypic vertebrate polyunsaturated fatty acids biosynthesis pathway.

Atlantic salmon postsmolts were fed a control diet or one of 9 experimental diets containing various blends of two vegetable oils, linseed (LO) and rapeseed oil (RO), and fish oil (FO) in a triangular trial design, for 50 wk. After sampling, fish previously fed 100% FO, LO and RO were switched to a diet containing 100% FO for a further 20 wk. Fatty acid compositions of flesh total lipid were linearly correlated with dietary fatty acid compositions (r = 0.99-1.00, P < 0.0001). Inclusion of vegetable oil at 33% of total oil significantly reduced the concentrations of the highly unsaturated fatty acids, eicosapentaenoate [20:5(n-3)] and docosahexaenoate [22:6(n-3)], to approximately 70 and 75%, respectively, of the values in fish fed 100% FO. When vegetable oil was included at 100% of total dietary lipid, the concentrations of 20:5(n-3) and 22:6(n-3) were significantly reduced to approximately 30 and 36%, respectively, of the values in fish fed FO. Transfer of fish previously fed 100% vegetable oil to a 100% FO diet for 20 wk restored the concentrations of 20:5(n-3) and 22:6(n-3) to approximately 80% of the value in fish fed 100% FO for 70 wk, although the values were still significantly lower. However, in fish previously fed either 100% LO or RO, concentrations of 18:2(n-6) remained approximately 50% higher than in fish fed 100% FO. This study suggests that RO and LO can be used successfully to culture salmon through the seawater phase of their growth cycle; this will result in reductions in flesh 20:5(n-3) and 22:6(n-3) concentrations that can be partially restored by feeding a diet containing only marine FO for a period before harvest.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by motoneuron degeneration and muscle paralysis. Although the precise pathogenesis of ALS remains unclear, mutations in Cu/Zn superoxide dismutase (SOD1) account for ∼20–25% of familial ALS cases, and transgenic mice overexpressing human mutant SOD1 develop an ALS-like phenotype. Evidence suggests that defects in axonal transport play an important role in neurodegeneration. In Legs at odd angles (Loa) mice, mutations in the motor protein dynein are associated with axonal transport defects and motoneuron degeneration. Here, we show that retrograde axonal transport defects are already present in motoneurons of SOD1G93A mice during embryonic development. Surprisingly, crossing SOD1G93A mice with Loa/+ mice delays disease progression and significantly increases life span in Loa/SOD1G93A mice. Moreover, there is a complete recovery in axonal transport deficits in motoneurons of these mice, which may be responsible for the amelioration of disease. We propose that impaired axonal transport is a prime cause of neuronal death in neurodegenerative disorders such as ALS.

Biosynthesis of the highly biologically active long-chain polyunsaturated fatty acids, arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids, in vertebrates requires the introduction of up to three double bonds catalyzed by fatty acyl desaturases (Fad). Synthesis of ARA is achieved by Δ6 desaturation of 18∶2n − 6 to produce 18∶3n − 6 that is elongated to 20∶3n − 6 followed by Δ5 desaturation. Synthesis of EPA from 18∶3n − 3 requires the same enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further elongations, a second Δ6 desaturation and a peroxisomal chain shortening step. This paper describes cDNAs, fad1 and fad2, isolated from the herbivorous, marine teleost fish (Siganus canaliculatus) with high similarity to mammalian Fad proteins. Functional characterization of the cDNAs by heterologous expression in the yeast Saccharomyces cerevisiae showed that Fad1 was a bifunctional Δ6∕Δ5 Fad. Previously, functional dual specificity in vertebrates had been demonstrated for a zebrafish Danio rerio Fad and baboon Fad, so the present report suggests bifunctionality may be more widespread in vertebrates. However, Fad2 conferred on the yeast the ability to convert 22∶5n − 3 to DHA indicating that this S. canaliculatus gene encoded an enzyme having Δ4 Fad activity. This is a unique report of a Fad with Δ4 activity in any vertebrate species and indicates that there are two possible mechanisms for DHA biosynthesis, a direct route involving elongation of EPA to 22∶5n − 3 followed by Δ4 desaturation, as well as the more complicated pathway as described above.Δ4 desaturase | bifunctional Δ6/Δ5 desaturase | polyunsaturated fatty acid biosynthesis | Siganus canaliculatus | teleost

Highly unsaturated fatty acid (HUFA) synthesis in Atlantic salmon (Salmo salar) was known to be influenced by both nutritional and environmental factors. Here we aimed to test the hypothesis that both these effectors involved similar molecular mechanisms. Thus, HUFA biosynthetic activity and the expression of fatty acyl desaturase and elongase genes were determined at various points during an entire two year production cycle in salmon fed diets containing either 100% fish oil or diets in which a high proportion (75% and 100%) of fish oil was replaced by C 18 polyunsaturated fatty acid-rich vegetable oil. The results showed that HUFA biosynthesis in Atlantic salmon varied during the growth cycle with peak activity around seawater transfer and subsequent low activities in seawater. Consistent with this, gene expression of Δ6 desaturase, the rate-limiting step in the HUFA biosynthetic pathway, was highest around the point of seawater transfer and lowest during the seawater phase. In addition, the expression of both Δ6 and Δ5 desaturase genes was generally higher in fish fed the vegetable oilsubstituted diets compared to fish fed fish oil, particularly in the seawater phase. Again, generally consistent with this, the activity of the HUFA biosynthetic pathway was invariably higher in fish fed diets in which fish oil was substituted by vegetable oil compared to fish fed only fish oil. In conclusion, these studies showed that both nutritional and environmental modulation of HUFA biosynthesis in Atlantic salmon involved regulation of fatty acid desaturase gene expression.3