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The synthesis rates of n‐3 and n‐6 polyunsaturated fatty acids (PUFAs) in rodents and humans are not agreed upon and depend on substrate availability independently of the capacity for synthesis. Therefore, we aimed to assess the activities of the enzymes for n‐3 and n‐6 PUFA synthesis pathways in liver, brain, testicle, kidney, heart, and lung, in relation to their protein concentration levels. Eight‐week‐old Balb/c mice (n = 8) were fed a standard chow diet (6.2% fat, 18.6% protein, and 44.2% carbohydrates) until 14 weeks of age, anesthetized with isoflurane and tissue samples were collected (previously perfused) and stored at −80°C. The protein concentration of the enzymes (Δ‐6D, Δ‐5D, Elovl2, and Elovl5) were assessed by ELISA kits; their activities were assayed using specific PUFA precursors and measuring the respective PUFA products as fatty acid methyl esters by gas chromatographic analysis. The liver had the highest capacity for PUFA biosynthesis, with limited activity in the brain, testicles, and kidney, while we failed to detect activity in the heart and lung. The protein concentration and activity of the enzymes were significantly correlated. Furthermore, Δ‐6D, Δ‐5D, and Elovl2 have a higher affinity for n‐3 PUFA precursors compared to n‐6 PUFA. The capacity for PUFA synthesis in mice mainly resides in the liver, with enzymes having preference for n‐3 PUFAs. [ABSTRACT FROM AUTHOR]

Epidemiological studies fairly convincingly suggest that higher intake of fish and omega-3 fatty acids present in fish is associated with reduced risk for age-related cognitive decline (ARCD). Normally, docosahexaenoic acid (DHA) in plasma is positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, ARCD is not consistently associated with lower plasma DHA. Furthermore, DHA is often slightly but significantly higher in plasma and erythrocytes in the elderly without ARCD compared to young adults. Higher plasma DHA in the elderly may be a sign that their fish or DHA intake is higher but we show here that various aspects of DHA homeostasis also change with age. Our supplementation and tracer studies show that DHA metabolism, e.g. transit through the plasma and apparent retroconversion but not beta-oxidation, is different in healthy elderly compared to healthy young adults. Apolipoprotein E4 increases the risk of ARCD, possibly in part because it changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may contribute to making the elderly more susceptible to cognitive decline despite them having similar or sometimes higher plasma DHA than in younger adults.

BACKGROUND: Omega-3 fatty acid (OM3) intake is associated with a lower risk of developing Alzheimer's disease, but individuals carrying the ɛ4 allele of apolipoprotein E (APOE4) might not benefit from this prevention strategy. Indeed, they might have lower OM3 into plasma free fatty acid (FFA) and lysophosphatidylcholine (LPC) compartments, the two forms the brain can take-in. OBJECTIVE: To evaluate the docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations in the FFA and LPC pre- and post-OM3 supplementation in APOE4 carriers and non-carriers. DESIGN: Plasma samples from 25 APOE4 carriers and non-carriers before and six months after receiving 2.5 g/d DHA+EPA daily were analyzed. DHA and EPA concentrations in the LPC, and FFA were compared by supplementation and genotype. A secondary analysis investigated the interaction between body mass index (BMI) and APOE genotype status. RESULTS: There was no genotype x supplement interaction nor a genotype effect on LPC and FFA. However, there was a supplement effect where OM3 increased in all lipid compartment by < 1-fold to 4-fold. Individuals with a low BMI had higher OM3 increase concentrations in the LPC than those with a high BMI. CONCLUSIONS: APOE4 carriers and non-carriers can both benefit from taking an OM3 supplement. However, individuals with a high BMI have lower OM3 increases than those with a lower BMI. [ABSTRACT FROM AUTHOR]

Dairy fat is rich in SFA such as palmitic acid (16:0) but low in linoleic acid (18:2n-6). The natural carbon 13 enrichment (δ13C) of 16:0 is higher in dairy fat than in most of the food supply. In adults, serum levels of pentadecanoic acid (15:0) and heptadecanoic acid (17:0) are recognised as biomarkers of dairy intake. In adolescents, no study has evaluated serum fatty acid levels or δ13C in response to chronic dairy consumption. The objectives of this study were to evaluate whether increased dairy product consumption can modulate (1) serum fatty acid levels and (2) 16:0 δ13C in adolescents with overweight/obesity who followed a 12-week weight management programme. This secondary analysis of a randomised control trial included two groups of adolescent females: recommended dairy (RDa; n 23) and low dairy (LDa; n 23). The RDa group was given 4 servings/d of dairy products while the LDa group maintained dairy intakes at ≤ 2 servings/d. Blood was sampled before and after the intervention. Lipids were extracted and separated, and fatty acids were quantified by GC. Isotope ratio MS was used to assess 16:0 δ13C. There were no group differences on serum changes of 15:0 or 17:0. Within TAG, 18:2n-6 was lowered by 7·4 % only in the RDa group (P = 0·040). The difference in delta 16:0 δ13C between the LDa and RDa groups did not reach statistical significance (P = 0·070). Reductions in serum 18:2n-6 by dairy consumption could have positive health implications, but more studies are needed to confirm this assertion. [ABSTRACT FROM AUTHOR]

Abstract Background Higher fish or higher docosahexaenoic acid (DHA) intake normally correlates positively with higher plasma DHA level, but recent evidence suggests that the positive relationship between intake and plasma levels of DHA is less clear in the elderly. Methods We compared the metabolism of 13C-DHA in six healthy elderly (mean - 77 y old) and six young adults (mean - 27 y old). All participants were given a single oral dose of 50 mg of uniformly labelled 13C-DHA. Tracer incorporation into fatty acids of plasma triglycerides, free fatty acids, cholesteryl esters and phospholipids, as well as apparent retroconversion and β-oxidation of 13C-DHA were evaluated 4 h, 24 h, 7d and 28d later. Results Plasma incorporation and β-oxidation of 13C-DHA reached a maximum within 4 h in both groups, but 13C-DHA was transiently higher in all plasma lipids of the elderly 4 h to 28d later. At 4 h post-dose, 13C-DHA β-oxidation was 1.9 times higher in the elderly, but over 7d, cumulative β-oxidation of 13C-DHA was not different in the two groups (35% in the elderly and 38% in the young). Apparent retroconversion of 13C-DHA was well below 10% of 13C-DHA recovered in plasma at all time points, and was 2.1 times higher in the elderly 24 h and 7d after tracer intake. Conclusions We conclude that 13C-DHA metabolism changes significantly during healthy aging. Since DHA is a potentially important molecule in neuro-protection, these changes may be relevant to the higher vulnerability of the elderly to cognitive decline.

Background: Plasma eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations increase with age. Objective: The aim of this study was to evaluate EPA and AA metabolism in young and old men by using uniformly labeled carbon-13 (13C) fatty acids. Design: Six young (~25 y old) and 6 old (~75 y old) healthy men were recruited. Each participant consumed a single oral dose of 35 mg 13C-EPA and its metabolism was followed in the course of 14 d in the plasma and 28 d in the breath. After the washout period of ≥28 d, the same participants consumed a single oral dose of 50 mg 13C-AA and its metabolism was followed for 28 d in plasma and breath. Results: There was a time × age interaction for 13C-EPA (Ptime × age = 0.008), and the shape of the postprandial curves was different between young and old men. The 13C-EPA plasma half-life was ~2 d for both young and old men (P = 0.485). The percentage dose recovered of 13C-EPA per hour as 13CO2 and the cumulative β-oxidation of 13C-EPA did not differ between young and old men. At 7 d, however, old men had a >2.2-fold higher plasma 13C-DHA concentration synthesized from 13C-EPA compared with young men (Page = 0.03). 13C-AA metabolism was not different between young and old men. The 13C-AA plasma half-life was ~4.4 d in both young and old participants (P = 0.589). Conclusions: The metabolism of 13C-AA was not modified by age, whereas 13C-EPA metabolism was slightly but significantly different in old compared with young men. The higher plasma 13C-DHA seen in old men may be a result of slower plasma DHA clearance with age. [ABSTRACT FROM AUTHOR]