Metabolism of n−3 and n−6 fatty acids in Atlantic salmon liver: Stimulation by essential fatty acid deficiency

Abstract

Oxidation, esterification, desaturation, and elongation of [1-14C]18:2n-6 and [1-14C]18:3n-3 were studied using hepatocytes from Atlantic salmon (Salmo salar L.) maintained on diets deficient in n-3 and n-6 polyunsaturated fatty acids (PUFA) or supplemented with n-3 PUFA. For both dietary groups, radioactivity from 18:3n-3 was incorporated into lipid fractions two to three times faster than from 18:2n-6, and essential fatty acids (EFA) deficiency doubled the incorporation. Oxidation to CO2 was very low and was independent of substrate or diet, whereas oxidation to acid-soluble products was stimulated by EFA deficiency. Products from 18:2n-6 were mainly 18:3n-6, 20:3n-6, and 20:4n-6, with minor amounts of 20:2n-6 and 22:5n-6. Products from 18:3n-3 were mainly 18:4n-3, 20:5n-3, and 22:6n-3, with small amounts of 20:3n-3. The percentage of 22:6n-3 in the polar lipid fraction of EFA-deficient hepatocytes was fourfold higher than in n-3 PUFA-supplemented cells. This correlated well with our other results obtained after abdominal injection of [1-14C]18:3n-3 and [1-14C]18:2n-6. In hepatocytes incubated with [4,5-3H]-22:6n-3, 20:5n-3 was the main product. This retroconversion was increased by EFA deficiency, as was peroxisomal betaoxidation activity. This study shows that 18:2n-6 and 18:3n-3 can be elongated and desaturated in Atlantic salmon liver, and that this conversion and the activity of retroconversion of very long chain PUFA is markedly enhanced by EFA deficiency.

Effects of essential fatty acid deficiency and supplementation with docosahexaenoic acid (DHA; 22:6n-3) on cellular fatty acid compositions and fatty acyl desaturation in a cell culture model

“…3,6 In a recent dietary trial, the incorporation of 18:2n-6 and 18:3n-3 was increased in hepatocytes from Atlantic salmon (Salmo salar) fed an EFA deficient diet compared to one fed an n-3-supplemented diet. 22 The present study has confirmed this result but also showed that prior supplementation of the cells with DHA did not affect the PUFA uptake and incorporation processes in either cell line. The present study was performed under conditions where neither cell line was metabolically predisposed to storing lipid.…”

“…36 To our knowledge the effects of EFA deficiency on retroconversion processes in cell cultures has not been reported previously, but retroconversion of DHA to EPA and 22:5n-3 was reported to be increased in hepatocytes prepared from salmon fed an EFA deficient diet in comparison with hepatocytes from salmon fed an n-3PUFA supplemented diet. 22 Prior supplementation with DHA also very significantly reduced the page 17 desaturation/elongation of [1- 14 C]18:3n-3 to tetraene and pentaene products in both cell lines.…”

“…Retroconversion of DHA to 22:5n-3 and EPA has been observed previously in various animal tissues [30][31][32] and retroconversion of DHA to 22:5n-3 and EPA, and 22:5n-3 to EPA has been reported in various cells in culture. 22,[33][34][35] In contrast, in rat U III (uterine stromal) cells, which show higher levels of DHA production from 18:3n-3 than most other cell lines, there was no significant retroconversion of DHA, added at 5 µM. 36 To our knowledge the effects of EFA deficiency on retroconversion processes in cell cultures has not been reported previously, but retroconversion of DHA to EPA and 22:5n-3 was reported to be increased in hepatocytes prepared from salmon fed an EFA deficient diet in comparison with hepatocytes from salmon fed an n-3PUFA supplemented diet.…”

Compared to fish oil alone, a corn and fish oil mixture decreases the lipid requirement of a freshwater fish species, Carassius auratus gibelio

“…The linearly increased relative contents of 18:2n−6 and 18:3n−3, and the logarithmic increased relative content of LC-PUFA observed in the present study may indicate that LC-PUFA biosynthesis in gibel carp decreases as dietary lipid concentrations increase. It has been demonstrated that the rates of conversion of 18:2n−6 and 18:3n−3 to LC-PUFA were enhanced by EFA deficiency, and the LC-PUFA supply in the diet potentially impairs the LC-PUFA synthesis pathway in vivo in some species (Ruyter and Thomassen, 1999;Sargent et al, 2002). When the same lipid source was used in the present study, the diets with higher lipid concentrations allowed the fish to receive greater absolute amounts of LC-PUFA, which may inhibit its biosynthesis in vivo.…”

Fatty acid metabolism in Atlantic salmon (Salmo salar L.) hepatocytes and influence of dietary vegetable oil

“…The affinity of the desaturation and elongation enzymes for fatty acids is higher for the n-3 series than for the n-6 and n-9 series [6,7]. Only a few studies have simultaneously investigated both the pathways of β-oxidation and desaturation/elongation of fatty acids [8][9][10], and very little has been done regarding the overall metabolic fate of fatty acids in cells. Previous studies on lipid metabolism in salmonids have mainly concentrated on the metabolism of 18:3n-3 [11], and effects of dietary treatment.…”