Association of the FADS2 gene with omega-6 and omega-3 PUFA Concentration in the egg yolk of Japanese quail

This study focused on the association of polymorphisms of the FADS2 gene with fatty acid profiles in egg yolk of eight Japanese quail lines selected for high and low omega-6:omega-3 PUFA ratio (h2 = 0.36-0.38). For the identification of polymorphisms within the FADS2 gene 1350 bp of cDNA sequence were obtained encoding 404 amino acids. Five synonymous SNPs were found by comparative sequencing of animals of the high and low lines. These SNPs were genotyped by single base extension on 160 Japanese quail. The association analysis, comprising analysis of variance and family based association test (FBAT), revealed significant effects of SNP3 and SNP4 genotypes on the egg yolk fatty acid profiles, especially the omega-6 and omega-3 PUFAs (P < 0.05). No effects of the other SNPs were found - indicating that these are not in linkage disequilibrium with the causal polymorphism. The results of this study promote FADS2 as a functional candidate gene for traits related to omega-6 and omega-3 PUFA concentration in the egg yolk.     

Genetic variants of the FADS gene cluster and ELOVL gene family, colostrums LC-PUFA levels, breastfeeding, and child cognition

Introduction

Breastfeeding effects on cognition are attributed to long-chain polyunsaturated fatty acids (LC-PUFAs), but controversy persists. Genetic variation in fatty acid desaturase (FADS) and elongase (ELOVL) enzymes has been overlooked when studying the effects of LC-PUFAs supply on cognition. We aimed to: 1) to determine whether maternal genetic variants in the FADS cluster and ELOVL genes contribute to differences in LC-PUFA levels in colostrum; 2) to analyze whether these maternal variants are related to child cognition; and 3) to assess whether children''s variants modify breastfeeding effects on cognition.

Methods

Data come from two population-based birth cohorts (n = 400 mother-child pairs from INMA-Sabadell; and n = 340 children from INMA-Menorca). LC-PUFAs were measured in 270 colostrum samples from INMA-Sabadell. Tag SNPs were genotyped both in mothers and children (13 in the FADS cluster, 6 in ELOVL2, and 7 in ELOVL5). Child cognition was assessed at 14 mo and 4 y using the Bayley Scales of Infant Development and the McCarthy Scales of Children''s Abilities, respectively.

Results

Children of mothers carrying genetic variants associated with lower FADS1 activity (regulating AA and EPA synthesis), higher FADS2 activity (regulating DHA synthesis), and with higher EPA/AA and DHA/AA ratios in colostrum showed a significant advantage in cognition at 14 mo (3.5 to 5.3 points). Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. Moreover, not being breastfed resulted in a disadvantage in cognition (5 to 8 points) among children CC homozygote for rs2397142 (low ELOVL5 activity), but not among those carrying the G allele.

Conclusion

Genetically determined maternal supplies of LC-PUFAs during pregnancy and lactation appear to be crucial for child cognition. Breastfeeding effects on cognition are modified by child genetic variation in fatty acid desaturase and elongase enzymes.     

Murine FATP alleviates growth and biochemical deficiencies of yeast fat1Delta strains.

Saccharomyces cerevisiae is an ideal model eukaryote for studying fatty-acid transport. Yeast are auxotrophic for unsaturated fatty acids when grown under hypoxic conditions or when the fatty-acid synthase inhibitor cerulenin is included in the growth media. The FAT1 gene encodes a protein, Fat1p, which is required for maximal levels of fatty-acid import and has an acyl CoA synthetase activity specific for very-long-chain fatty acids suggesting this protein plays a pivotal role in fatty-acid trafficking. In the present work, we present evidence that Fat1p and the murine fatty-acid transport protein (FATP) are functional homologues. FAT1 is essential for growth under hypoxic conditions and when cerulenin was included in the culture media in the presence or absence of unsaturated fatty acids. FAT1 disruptants (fat1Delta) fail to accumulate the fluorescent long-chain fatty acid fatty-acid analogue 4, 4-difluoro-5-methyl-4-bora-3a,4a-diaza-s-indacene-3-do decanoic acid (C1-BODIPY-C12), have a greatly diminished capacity to transport exogenous long-chain fatty acids, and have very long-chain acyl CoA synthetase activities that were 40% wild-type. The depression in very long-chain acyl CoA synthetase activities were not apparent in cells grown in the presence of oleate. Additionally, beta-oxidation of exogenous long-chain fatty acids is depressed to 30% wild-type levels. The reduction of beta-oxidation was correlated with a depression of intracellular oleoyl CoA levels in the fat1Delta strain following incubation of the cells with exogenous oleate. Expression of either Fat1p or murine FATP from a plasmid in a fat1Delta strain restored these phenotypic and biochemical deficiencies. Fat1p and FATP restored growth of fat1Delta cells in the presence of cerulenin and under hypoxic conditions. Furthermore, fatty-acid transport was restored and was found to be chain length specific: octanoate, a medium-chain fatty acid was transported in a Fat1p- and FATP-independent manner while the long-chain fatty acids myristate, palmitate, and oleate required either Fat1p or FATP for maximal levels of transport. Lignoceryl CoA synthetase activities were restored to wild-type levels in fat1Delta strains expressing either Fat1p or FATP. Fat1p or FATP also restored wild-type levels of beta-oxidation of exogenous long-chain fatty acids. These data show that Fat1p and FATP are functionally equivalent when expressed in yeast and play a central role in fatty-acid trafficking.     

植物合成长链多不饱和脂肪酸研究进展

长链不饱和脂肪酸（LC-PUFAs）对人类健康具有重要作用,通过转基因植物生产LC-PUFAs具有低成本、可持续、污染少等诸多优势。本文简要介绍了LC-PUFAs的作用、来源及其植物生物合成途径,综述了转基因植物合成LC-PUFAs的研究进展,并对如何进一步提高LC-PUFAs产量进行了探讨。     

Gestational diabetes mellitus decreases placental uptake of long-chain polyunsaturated fatty acids: involvement of long-chain acyl-CoA synthetase

The long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic (AA) and docosahexaenoic (DHA) acids are essential for fetal development. Gestational diabetes mellitus (GDM) is a pregnancy disorder associated with perinatal and lifelong risk complications for both the mother and the newborn. Our aim was to investigate the influence of GDM, and some of its associated conditions, upon the placental uptake of AA and DHA. Uptake of ¹⁴C-AA and ¹⁴C-DHA by human trophoblasts obtained from normal pregnancies (NTB cells) was mediated by both saturable (for lower substrate concentrations) and non-saturable (for higher substrate concentrations) mechanisms. Uptake of both fatty acids was inhibited by other LC-PUFAs and, markedly, by the long-chain acyl-CoA synthetase (ACSL) inhibitor, triacsin C. Human trophoblasts obtained from GDM pregnancies (DTB cells) showed a significantly lower ¹⁴C-AA and ¹⁴C-DHA accumulation, through a decrease in both the saturable and the non-saturable components of uptake, which was associated with a decrease in ACSL1 mRNA levels. Uptake of LC-PUFAs by NTB cells increased (by 20–25%) after short-term exposure to TNF-α (¹⁴C-AA and ¹⁴C-DHA) and insulin (¹⁴C-DHA). In conclusion, GDM, distinctly from its associated conditions, markedly decreases placental uptake of LC-PUFAs, which probably contributes to the deleterious effects of this disease for the newborn.     

Adaptive Evolution of the FADS Gene Cluster within Africa

Long chain polyunsaturated fatty acids (LC-PUFAs) are essential for brain structure, development, and function, and adequate dietary quantities of LC-PUFAs are thought to have been necessary for both brain expansion and the increase in brain complexity observed during modern human evolution. Previous studies conducted in largely European populations suggest that humans have limited capacity to synthesize brain LC-PUFAs such as docosahexaenoic acid (DHA) from plant-based medium chain (MC) PUFAs due to limited desaturase activity. Population-based differences in LC-PUFA levels and their product-to-substrate ratios can, in part, be explained by polymorphisms in the fatty acid desaturase (FADS) gene cluster, which have been associated with increased conversion of MC-PUFAs to LC-PUFAs. Here, we show evidence that these high efficiency converter alleles in the FADS gene cluster were likely driven to near fixation in African populations by positive selection ∼85 kya. We hypothesize that selection at FADS variants, which increase LC-PUFA synthesis from plant-based MC-PUFAs, played an important role in allowing African populations obligatorily tethered to marine sources for LC-PUFAs in isolated geographic regions, to rapidly expand throughout the African continent 60–80 kya.     

Fermentation performance and metabolomic analysis of an engineered high-yield PUFA-producing strain of Schizochytrium sp.

Bioprocess and Biosystems Engineering - The ω-3/long-chain polyunsaturated fatty acids (LC-PUFAs) play an important role in human health, but they cannot be synthesized in sufficient amounts...     

Rational metabolic engineering of transgenic plants for biosynthesis of omega-3 polyunsaturates

The health-beneficial effects of long-chain polyunsaturated fatty acids (LC-PUFAs), derived mainly from fish oil, coupled with the growing requirement for an alternative and sustainable source of these compounds, has led to efforts to engineer oilseed crops for their production. LC-PUFA synthesis has been achieved using combinations of heterologous endomembrane desaturases and elongases expressed in model oilseed plants. Two general approaches have been employed that both use endogenous 18 carbon fatty acids as the starting substrates: the Delta6- and Delta8-pathways, which perform desaturation followed by elongation or elongation followed by desaturation, respectively. However, yields above 20% have not yet been realized owing to bottlenecks that become apparent in the endogenous biosynthetic pathways when heterologous genes are expressed. These bottlenecks might be caused partly by inefficient non-native enzymes in the host system or also by suboptimal acyl-exchange mechanisms between the acyl-CoA and lipid class pools. The fine-tuning of the fatty acid flux between the acyl-CoA, phospholipid, and triacylglycerol pools will be essential to maximise polyunsaturated fatty acid yields in seed oils. In addition, efficient substrate channelling and lipid synthesis could depend on specific endoplasmic reticulum subdomain localisation for key endogenous enzymes, and this organization could be compromised in heterologous systems.     

Role of omega-3 fatty acids in obesity, metabolic syndrome, and cardiovascular diseases: a review of the evidence

The present review aims to illustrate current knowledge about the efficacy of omega-3 long-chain polyunsaturated fatty acids (n?3 LC-PUFAs) in treating/preventing several metabolic pathologies. We reviewed systematically the published evidence on the effectiveness of n?3 LC-PUFAs fish consumption or n?3 LC-PUFAs supplementation on prevention/treatment of obesity, metabolic syndrome, and cardiovascular diseases. Most of the reviewed studies were randomized-controlled interventional trials, although some relevant prospective and cross-sectional studies as well as some meta-analysis were also reviewed. Supplementation with n?3 LC-PUFAs might improve some obesity-associated metabolic syndrome features such as insulin resistance, hypertension and dyslipidemia by decreasing plasma triglycerides. Moreover, the blood pressure-lowering and anti-inflammatory properties of these fatty acids and their benefits in vascular function might confer cardioprotection. However, the efficacy of n?3 LC-PUFA on reducing myocardial infarction, arrhythmia, cardiac and sudden death, or stroke is controversial. Due to the beneficial actions of n?3 LC-PUFAs, several worldwide government and health organizations have established some recommendations of n?3 LC-PUFAs intake for groups of population. In general, the recommended levels for diseases prevention are lower than those advised for particular treatments. However, more clinical trials are necessary to recommend the most effective dosages and formulas (type of n?3 LC-PUFA, EPA/DHA ratio) for specific pathologies.     

High contents of very long-chain polyunsaturated fatty acids in different moss species

Key message

Mosses have high contents of polyunsaturated fatty acids. Tissue-specific differences in fatty acid contents and fatty acid desaturase (FADS)-encoding gene expression exist. The arachidonic acid-synthesizing FADS operate in the ER.

Abstract

Polyunsaturated fatty acids (PUFAs) are important cellular compounds with manifold biological functions. Many PUFAs are essential for the human diet and beneficial for human health. In this study, we report on the high amounts of very long-chain (vl) PUFAs (≥C₂₀) such as arachidonic acid (AA) in seven moss species. These species were established in axenic in vitro culture, as a prerequisite for comparative metabolic studies under highly standardized laboratory conditions. In the model organism Physcomitrella patens, tissue-specific differences in the fatty acid compositions between the filamentous protonema and the leafy gametophores were observed. These metabolic differences correspond with differential gene expression of fatty acid desaturase (FADS)-encoding genes in both developmental stages, as determined via microarray analyses. Depending on the developmental stage and the species, AA amounts for 6–31 %, respectively, of the total fatty acids. Subcellular localization of the corresponding FADS revealed the endoplasmic reticulum as the cellular compartment for AA synthesis. Our results show that vlPUFAs are highly abundant metabolites in mosses. Standardized cultivation techniques using photobioreactors along with the availability of the P. patens genome sequence and the high rate of homologous recombination are the basis for targeted metabolic engineering in moss. The potential of producing vlPUFAs of interest from mosses will be highlighted as a promising area in plant biotechnology.     

Cardiovascular disease and long-chain omega-3 fatty acids

PURPOSE OF REVIEW: Of all known dietary factors, long-chain omega-3 fatty acids may be the most protective against death from coronary heart disease. New evidence has confirmed and refined the cardioprotective role of these fatty acids. RECENT FINDINGS: Omega-3 fatty acid supplementation reduces the risk of sudden cardiac death and death from any cause within 4 months in post-myocardial infarction patients. Evidence continues to accrue for benefits in the primary prevention of coronary heart disease and stroke, and an anti-arrhythmogenic mechanism is emerging as the most likely explanation. SUMMARY: Current evidence suggests that individuals with coronary artery disease may reduce their risk of sudden cardiac death by increasing their intake of long-chain omega-3 fatty acids by approximately 1 g per day.     

Effect of a conjugated linoleic acid and omega-3 fatty acid mixture on body composition and adiponectin

This study aimed to determine the effect of supplementation with conjugated linoleic acids (CLAs) plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) on body composition, adiposity, and hormone levels in young and older, lean and obese men. Young (31.4+/-3.9 years) lean (BMI, 23.6+/-1.5 kg/m2; n=13) and obese (BMI, 32.4+/-1.9 kg/m2; n=12) and older (56.5+/-4.6 years) lean (BMI, 23.6+/-1.5 kg/m2; n=20) and obese (BMI, 32.0+/-1.6 kg/m2; n=14) men participated in a double-blind placebo-controlled, randomized crossover study. Subjects received either 6 g/day control fat or 3 g/day CLA (50:50 cis-9, trans-11:trans-10, cis-12) and 3 g/day n-3 LC-PUFA for 12 weeks with a 12-week wash-out period between crossovers. Body composition was assessed by dual-energy X-ray absorptiometry. Fasting adiponectin, leptin, glucose, and insulin concentrations were measured and insulin resistance estimated by homeostasis model assessment for insulin resistance (HOMA-IR). In the younger obese subjects, CLA plus n-3 LC-PUFA supplementation compared with control fat did not result in increased abdominal fat and raised both fat-free mass (2.4%) and adiponectin levels (12%). CLA plus n-3 LC-PUFA showed no significant effects on HOMA-IR in any group but did increase fasting glucose in older obese subjects. In summary, supplementation with CLA plus n-3 LC-PUFA prevents increased abdominal fat mass and raises fat-free mass and adiponectin levels in younger obese individuals without deleteriously affecting insulin sensitivity, whereas these parameters in young and older lean and older obese individuals were unaffected, apart from increased fasting glucose in older obese men.     

Metabolic effects of intravenous LCT or MCT/LCT lipid emulsions in preterm infants

Most lipid emulsions for parenteral feeding of premature infants are based on long-chain triacylglycerols (LCTs), but inclusion of medium-chain triacylglycerols (MCTs) might provide a more readily oxidizable energy source. The influence of these emulsions on fatty acid composition and metabolism was studied in 12 premature neonates, who were randomly assigned to an LCT emulsion (control) or an emulsion with a mixture of MCT and LCT (1:1). On study day 7, all infants received [13C]linoleic (LA) and [13C]alpha-linolenic acid (ALA) tracers orally. Plasma phospholipid (PL) and triacylglycerol (TG) fatty acid composition and 13C enrichments of plasma PL fatty acids were determined on day 8. After 8 days of lipid infusion, plasma TGs in the MCT/LCT group had higher contents of C8:0 (0.50 +/- 0.60% vs. 0.10 +/- 0.12%; means +/- SD) and C10:0 (0.66 +/- 0.51% vs. 0.15 +/- 0.17%) than controls. LA content of plasma PLs was slightly lower in the MCT/LCT group (16.47 +/- 1.16% vs. 18.57 +/- 2.09%), whereas long-chain polyunsaturated derivatives (LC-PUFAs) of LA and ALA tended to be higher. The tracer distributions between precursors and products (LC-PUFAs) were not significantly different between groups. Both lipid emulsions achieve similar plasma essential fatty acid (EFA) contents and similar proportional conversion of EFAs to LC-PUFAs. The MCT/LCT emulsion seems to protect EFAs and LC-PUFAs from beta-oxidation.     

LC-PUFA from photosynthetic microalgae: occurrence, biosynthesis, and prospects in biotechnology

Microalgae offer potential for numerous commercial applications, among them the production of long-chain polyunsaturated fatty acids (LC-PUFAs). These valuable fatty acids are important for a variety of nutraceutical and pharmaceutical purposes, and the market for these products is continually growing. An appropriate ratio of LC-PUFA of the ω-3 and ω-6 groups is vital for "healthy" nutrition, and adequate dietary intake has strong health benefits in humans. Microalgae of diverse classes are primary natural producers of LC-PUFA. This mini-review presents an introductory overview of LC-PUFA-related health benefits in humans, describes LC-PUFA occurrence in diverse microalgal classes, depicts the major pathways of their biosynthesis in microalgae, and discusses the prospects for microalgal LC-PUFA production.     

A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle

Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype–phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 × 10^?6) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 × 10^?6), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.     

Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers

The relationship between high fish consumption and low mortality following coronary heart disease (CHD) and low incidence of breast cancer was first mentioned 3 decades ago. The fishes of interest are rich in omega-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could be the active nutrients. The current consensus about cardioprotection is that ω-3 LC-PUFAs would mainly exert antiarrhythmic effects. One of the proposed mechanisms is that circulating non-esterified LC-PUFAs partition into cardiac cells membrane phospholipids and exert a direct effect on ionic channels and/or modify intracellular calcium homeostasis. In another hypothesis, changes in the metabolism of phosphoinositides would be involved and lead to the differential activation of PKC isoforms. As compared to the mechanisms proposed for the cardioprotective effects of omega-3 LC-PUFAs, less is known about the molecular mechanisms involved in breast cancers prevention. Some proposed mechanisms such as the modulation of phosphoinositides metabolism and/or modulation of intracellular calcium homeostasis, are common to both pathologies. Other hypotheses involve the alteration of the cellular redox status induced by highly peroxidizable polyunsaturated fatty acids (FA), or the modulation of gene expression, both phenomena being tightly linked to apoptosis. In this review, we report and compare some proposed mechanisms for the involvement of omega-3 LC-PUFAs in both cardiac and breast cancer protection. Deliberately, we chose to discuss only the mechanisms, which are less described in other reviews such as ionic channels in cancer, calcium homeostasis, PKC activation or matrix metalloproteinases in both cancer and cardiac models. The leitmotiv along this review is that cardio- and cancero-protective effects use common pathways. Comparison of the cellular effects might therefore help to highlight the “protective” pathways.