Freshwater, Landlocked Grand Lake Strain of Atlantic Salmon (Salmo salar L.) as a Potential Genetic Source of Long Chain Polyunsaturated Fatty Acids Synthesis

Selection efforts focused on adaptation to plant-based diets, particularly the ability to synthesize polyunsaturated fatty acids (PUFA), are now emerging in aquaculture. Landlocked salmon (Grand Lake population; GL) may differ from the commercial Saint John River (SJR) strain in terms of PUFA metabolism. The objective of this study was to determine if GL salmon can contribute toward broodstock selection for enhanced PUFA synthesis. Two diets containing either fish oil (FO) or plant-based oil (FO-free) were fed to the SJR and GL strains (∼58 g/fish) for 16 weeks. Growth, liver, and muscle fatty acid (FA) content, and transcript expression of lipid metabolism and inflammation-related genes were evaluated. GL salmon fed the FO diet showed reduced growth compared to SJR salmon (fed either diet); however, GL salmon fed the FO-free diet, growth was not significantly different compared to any group. In liver, SJR salmon fed the FO-free diet had higher levels of n-6 PUFAs (21.9%) compared to GL fed the same diet (15.9%); while GL salmon fed the FO-free diet had higher levels of monounsaturated FAs (48.9%) compared with SJR salmon fed the same diet (35.7%). 20:5n-3 and 22:6n-3 were the same in GL and SJR salmon liver and muscle, respectively, fed the FO-free diet. In liver, GL salmon fed the FO-free diet had higher acac and acly compared to all treatments and had higher fasb compared to both strains fed the FO-diet. GL salmon fed the FO-free diet had higher cd36c and fabp3b in liver compared to GL salmon fed the FO diet and SJR salmon fed either diet. GL salmon fed the FO-free diet had higher lect2a and pgds in liver compared to SJR salmon fed the FO-free diet. In muscle, GL salmon fed the FO-free diet had higher fadsd5 and fadsd6b compared with both strains fed the FO diet. These results suggest there is a genetic basis behind the potential for GL salmon to utilize FO-free diets more efficiently than SJR salmon, with regards to FA metabolism.

Associations Between Vitamin B6 Status and Plasma Polyunsaturated Fatty Acids Among US Older Adults: NHANES 2003−2004

Objectives Previous evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP < 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. Methods A cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003−2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. Results Plasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8−2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0−4.33, P = 0.049, respectively]. Conclusions In US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding Sources No funding sources.

Impact of rs174537 on Critically Ill Patients with Acute Lung Injury: A Secondary Analysis of the OMEGA Randomized Clinical Trial

ABSTRACT Background Nutrition in the intensive care unit is vital for patient care; however, immunomodulatory diets rich in PUFAs like γ-linolenic acid (GLA), EPA, and DHA remain controversial for patients with acute respiratory distress syndrome. We postulate that genetic variants impacting PUFA metabolism contribute to mixed responses to PUFA-rich diets. Objectives In this study, we aimed to test the effects of single nucleotide polymorphism (SNP) rs174537 on differential responses to PUFA-rich diets. Methods We performed a secondary analysis of the OMEGA trial (NCT00609180) where 129 subjects received placebo control diets and 143 received omega-oil. DNA was extracted from buffy coats and used to genotype rs174537; plasma was used to quantitate PUFAs. We tested for SNP–diet interactions on PUFA concentrations, inflammatory biomarkers, and patient outcomes. Results We observed that all individuals receiving omega-oil displayed significantly higher concentrations of GLA, EPA, and DHA (all P < 0.0001), but they did not vary by genotype at rs174537. Statistically significant SNP–diet interactions were observed on circulating DHA concentrations in African Americans. Specifically, African American T-allele carriers on placebo illustrated elevated DHA concentrations. Additionally, all individuals receiving omega-oil had higher concentrations of EPA-derived urinary F3-isoprostane (Caucasians: P = 0.0011; African Americans: P = 0.0002). Despite these findings, we did not detect any significant SNP–diet interactions on pulmonary functional metrics, clinical outcomes, and mortality. Conclusions This study highlights the importance of genetic and racial contributions to PUFA metabolism and inflammation. In particular, rs174537 had a significant impact on circulating DHA and urinary isoprostane concentrations. Given our relatively small sample size, further investigations in larger multiethnic cohorts are needed to evaluate the impact of rs174537 on fatty acid metabolism and downstream inflammation.

Association of Polyunsaturated Fatty Acids and Vitamin B6 with Inflammation in Adults from the National Health and Nutrition Examination Survey (NHANES) 2003–2004

Objectives Polyunsaturated fatty acids (PUFA) such as n-3 PUFA, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n-6 PUFA, arachidonic acid (AA) may mediate inflammatory responses. Vitamin B6 deficiency has been shown to alter plasma PUFA levels. This perturbation of PUFA metabolism in vitamin B6 deficiency measured by pyridoxal-5’-phosphate (PLP) may contribute to inflammation. Thus, we aimed to examine the associations of 1) dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level, 2) plasma AA/(EPA + DHA) and PLP with C-reactive protein (CRP), a marker for inflammation, and 3) dietary EPA + DHA, and vitamin B6 with CRP level, using NHANES. Methods NHANES datasets (2003–2004) with subjects ≥20 years were analyzed, accounting for survey design and sample weights (n = 4486). The significance level was P < 0.05. Covariates were age, gender, ethnicity, BMI, smoking, alcohol, total energy, dietary supplements, physical activity, and NSAIDs, depending on analyses. Multiple linear regression assessed the association of dietary EPA + DHA, and vitamin B6 with plasma ratio of AA/(EPA + DHA) by PLP level (Low: < 20 nmol/L, High: ≥20 nmol/L). Next, multivariate logistic regression predicted the associations of plasma AA/(EPA + DHA) and PLP with CRP level (Low: ≤3 mg/L, Moderate to High: > 3 mg/L); then, dietary EPA + DHA, and B6 with CRP level. Results In the low PLP level, dietary EPA + DHA was negatively associated with plasma ratio of AA/(EPA + DHA) (B = ─5.29, SE = 0.84, P = < .0001), but B6 intake was not, whereas, in the high PLP level, both dietary EPA + DHA (B = ─2.99, SE = 0.53, P = < .0001) and dietary vitamin B6 (B = ─0.21, SE = 0.04, P = 0.0001) were inversely associated with plasma AA/(EPA + DHA). Further, low PLP level was associated with greater odds of moderate to high CRP level compared to high PLP level (adjusted OR (aOR): 2.8, 95% CI: 1.93–4.04, P = < .0001), but plasma AA/(EPA + DHA) was not. In addition, both dietary EPA + DHA (aOR: 0.5, 95% CI: 0.23–0.98, P = 0.04) and vitamin B6 (aOR: 0.8, 95% CI: 0.68–0.95, P = 0.009) were inversely associated with moderate to high CRP level. Conclusions Our findings show that low plasma PLP level and low vitamin B6 intake are associated with inflammation, and the relationship may be through their effect on PUFA metabolism, suggesting that increased intake of vitamin B6 and EPA and DHA may protect against inflammation. Funding Sources N/A.

Plasma 25-Hydroxyvitamin D Concentrations are Associated with Polyunsaturated Fatty Acid Metabolites in Young Children: Results from the Vitamin D Antenatal Asthma Reduction Trial

Vitamin D deficiency contributes to a multitude of health conditions, but its biological mechanisms are not adequately understood. Untargeted metabolomics offers the opportunity to comprehensively examine the metabolic profile associated with variations in vitamin D concentrations. The objective of the current analysis was to identify metabolites and metabolic pathways associated with plasma 25-hydroxyvitamin D [25(OH)D] concentrations. The current study included children of pregnant women in the Vitamin D Antenatal Asthma Reduction Trial, who had 25(OH)D and global metabolomics data at age 1 and 3 years. We assessed the cross-sectional associations between individual metabolites and 25(OH)D using linear regression adjusting for confounding factors. Twelve metabolites were significantly associated with plasma 25(OH)D concentrations at both age 1 and 3 after correction for multiple comparisons, including three members of the n-6 polyunsaturated fatty acid (PUFA) metabolism pathway (linoleate, arachidonate, and docosapentaenoate) inversely associated with 25(OH)D. These PUFAs along with four other significant metabolites were replicated in the independent Childhood Asthma Management Program (CAMP) cohort. Both vitamin D and n-6 PUFAs are involved in inflammatory processes, and evidence from cell and animal studies demonstrate a plausible biological mechanism where the active form of 25(OH)D may influence n-6 PUFA metabolism. These relationships warrant further investigation in other populations.

Revisiting the Role of LXRs in PUFA Metabolism and Phospholipid Homeostasis

Liver X receptors (LXRs) play a pivotal role in fatty acid (FA) metabolism. So far, the lipogenic consequences of in vivo LXR activation, as characterized by a major hepatic steatosis, has constituted a limitation to the clinical development of pharmacological LXR agonists. However, recent studies provided a different perspective. Beyond the quantitative accumulation of FA, it appears that LXRs induce qualitative changes in the FA profile and in the distribution of FAs among cellular lipid species. Thus, LXRs activate the production of polyunsaturated fatty acids (PUFAs) and their distribution into phospholipids via the control of FA desaturases, FA elongases, lysophosphatidylcholine acyltransferase (LPCAT3), and phospholipid transfer protein (PLTP). Therefore, LXRs control, in a dynamic manner, the PUFA composition and the physicochemical properties of cell membranes as well as the release of PUFA-derived lipid mediators. Recent studies suggest that modulation of PUFA and phospholipid metabolism by LXRs are involved in the control of lipogenesis and lipoprotein secretion by the liver. In myeloid cells, the interplay between LXR and PUFA metabolism affects the inflammatory response. Revisiting the complex role of LXRs in FA metabolism may open new opportunities for the development of LXR modulators in the field of cardiometabolic diseases.