Cardiometabolic Risk Factors at 5 Years After Omega-3 Fatty Acid Supplementation in Infancy.

BACKGROUND: Omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during infancy may reduce adult cardiovascular risk as observed in animals. We assessed the effect of n-3 LCPUFA supplementation in infancy on growth, body composition, and cardiometabolic risk factors at 5 years of age. METHODS: Infants were randomly assigned to a daily supplement of n-3 LCPUFA or olive oil (control) from birth to 6 months (n = 420). Measurements included weight, length, cord blood adipokines at birth and anthropometry, skinfolds, blood pressure, heart rate, fasting blood adipokines, and biochemistry at 5 years. RESULTS: The infants who received n-3 LCPUFA had a smaller waist circumference at 5 years (coefficient: 1.1 cm; 95% confidence interval [CI]: 0.01 to 2.14), which remained significant after adjustments for confounders (coefficient: 0.8 cm; 95% CI: 0.19 to 1.30). Five-year-old boys who received n-3 LCPUFA supplementation as infants had a 21% reduction in insulin concentrations (ratio: 0.79; 95% CI: 0.66 to 0.94) and a 22% reduction in insulin resistance (ratio: 0.78; 95% CI: 0.64 to 0.95) compared with the control group. There were no other differences in growth and cardiometabolic risk factors between the groups for the whole cohort at birth, 2.5, or 5 years. CONCLUSIONS: Supplementation with n-3 LCPUFA in infancy revealed a reduction in waist circumference at 5 years. Boys in the n-3 LCPUFA group showed reduced insulin concentrations and insulin resistance at 5 years, which may have beneficial outcomes for later health. No effects were seen in girls. Longer term follow-up of the cohort is warranted to determine whether these differences are maintained into adolescence.

Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at birth and 12 years of age: a double-blind, randomised controlled clinical trial.

Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPM) generated from the n-3 fatty acids EPA and DHA. n-3 Fatty acid supplementation during pregnancy may provide an intervention strategy to modify these novel SPM. This study aimed to assess the effect of n-3 fatty acid supplementation in pregnancy on offspring SPM at birth and 12 years of age (12 years). In all, ninety-eight atopic pregnant women were randomised to 3·7 g daily n-3 fatty acids or a control (olive oil), from 20 weeks gestation until delivery. Blood was collected from the offspring at birth and at 12 years. Plasma SPM consisting of 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), 10 S,17S-dihydroxydocosahexaenoic acid, maresins and protectin 1, were measured by liquid chromatography-tandem MS. We identified the resolvins RvE1, RvE2, RvE3, RvD1, 17R-RvD1 and RvD2 for the first time in human cord blood. n-3 Fatty acids increased cord blood 18-HEPE (P<0·001) derived from EPA relative to the control group. DHA-derived 17-HDHA at birth was significantly increased in the n-3 fatty acid group relative to the controls (P=0·001), but other SPM were not different between the groups. n-3 Fatty acid supplementation during pregnancy was associated with an increase in SPM precursors in the offspring at birth but the effects were not sustained at 12 years. The presence of these SPM, particularly at birth, may have functions relevant in the newborn that remain to be established, which may be useful for future investigations.

Cloning and characterization of two glutathione peroxidase cDNAs from southern bluefin tuna (Thunnus maccoyii).

Glutathione peroxidases (GPXs; EC 1.11.19) are key enzymes in the antioxidant defence systems of living organisms, including fish. Here we report the cloning of two GPX cDNAs from southern bluefin tuna (SBT, Thunnus maccoyii). One encodes a GPX1 or classical GPX and the other encodes a GPX4 or phospholipid hydroperoxide GPX. The 898 base-pair (bp) SBT GPX1 cDNA (GenBank accession no. EF452497) includes the complete protein coding region plus 35bp of the 5'-untranslated region (5'-UTR) and 296bp of the 3'-untranslated region (3'-UTR). The 974bp SBT GPX4 cDNA (GenBank accession no. EF452498) includes the complete protein coding region plus 101bp of the 5'-UTR and 306bp of the 3'-UTR. Both cDNAs contain a selenocysteine (Sec) codon in the protein coding region and a selenocysteine insertion sequence (SECIS) element in the 3'-UTR. The SBT GPX4 cDNA may encode a mitochondrial targeting sequence. A deduced amino acid sequence comparison revealed that the SBT GPX1 sequence was 67% identical to a human GPX1 sequence (GenBank accession no. X13709) and 69-83% identical to other fish GPX1 sequences. Similarly, the SBT GPX4 sequence was 63% identical to a human GPX4 sequence (GenBank accession no. BC046163) and 72-93% identical to other fish GPX4 sequences. GPX1 and GPX4 gene expressions and total GPX enzyme activity were investigated in SBT liver, muscle, kidney, spleen, heart, stomach, gill and pyloric caeca. Expression of the two genes varied from one tissue to the next and roughly paralleled the inter-tissue variation in GPX enzyme activity. The results are discussed in relation to possible roles for GPX1 and GPX4 genes in antioxidant defense in SBT.

Cloning and functional characterisation of a fatty acyl elongase from southern bluefin tuna (Thunnus maccoyii).

The synthesis of long chain polyunsaturated fatty acids (LCPUFA), such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), involves fatty acyl desaturase and elongase enzymes. The marine fish species southern bluefin tuna (SBT) can accumulate large quantities of omega-3 (n-3) LCPUFA in its flesh but their capacity to synthesize EPA and DHA is uncertain. A cDNA, sbtElovl5, encoding a putative fatty acyl elongase was amplified from SBT liver tissue. The cDNA included an open reading frame (ORF) encoding 294 amino acids. Sequence comparisons and phylogenetic analyses revealed a high level of sequence conservation between sbtElovl5 and fatty acyl elongase sequences from other fish species. Heterologous expression of the sbtElovl5 ORF in Saccharomyces cerevisiae confirmed that it encoded a fatty acyl elongase capable of elongating C(18/20) polyunsaturated fatty acid (PUFA) substrates, but not C(22) PUFA substrates. For the first time in an Elovl5, the substrate competition occurring in nature was investigated. Higher activity towards n-3 PUFA substrates than omega-6 (n-6) PUFA substrates was exhibited, regardless of substrate chain length. The sbtElovl5 preferentially elongated 18:4n-3 and 18:3n-6 rather than 20:5n-3 and 20:4n-6. The sbtElovl5 enzyme also elongated saturated and monounsaturated fatty acids.