Effects of polyunsaturated fatty acid intake and status during pregnancy,lactation, and early childhood on cardiometabolic health: A systematic review

The importance of polyunsaturated fatty acid (PUFA) intake in fetal life and infancy has been widely studied in relation to child cognitive and visual development, but whether early life PUFA exposure is related to cardiometabolic risk factors is unclear. The focus of this systematic review was to evaluate the effects of PUFA dietary intake and blood levels during pregnancy, lactation, or early childhood (⩽5 y) on obesity, blood pressure, blood lipids, and insulin sensitivity. We identified 4302 abstracts in the databases Embase, Medline and Cochrane Central (April 2014), of which 56 articles, reporting on 45 unique studies, met all selection criteria. Many of the included studies focused on obesity as an outcome (33 studies), whereas studies on insulin sensitivity were relatively scarce (6 studies). Overall, results for obesity, blood pressure, and blood lipids were inconsistent, with a few studies reporting effects in opposite directions and other studies that did not observe any effects of PUFAs on these outcomes. Four studies suggested beneficial effects of PUFAs on insulin sensitivity. We conclude that there is insufficient evidence to support a beneficial effect of PUFAs in fetal life or early childhood on obesity, blood pressure, or blood lipids. More research is needed to investigate the potential favorable effects of PUFAs on insulin sensitivity, and to examine the role of specific fatty acids in early life on later cardiometabolic health.     

Protective effect of eicosapentaenoic acid on palmitate-induced apoptosis in neonatal cardiomyocytes

Long chain polyunsaturated fatty acids (PUFAs) play an important role in cardioprotection. These effects have been largely attributed to membrane docosahexaenoic acid. Conversely, saturated fatty acids trigger apoptosis in cardiomyocytes, with modifications of mitochondrial properties including cardiolipin loss, cytochrome c release and caspase-3 activation. The purpose of this study was to investigate the chronic effect of eicosapentaenoic acid (EPA) on mitochondrial apoptosis induced by palmitate treatment and the associated signalling pathways. Confluent cultures of rat neonatal cardiomyocytes were treated for 2 days in media enriched with either EPA or arachidonic acid (AA) and then exposed to palmitate (0.5 mM) to induce apoptosis, in the absence of PUFA supplements. The EPA treatment resulted in significant membrane enrichment in n-3 PUFAs, especially in docosapentaenoic acid (DPA), and a large decrease in AA. Both AA and EPA treatments prevented caspase-3 activation, translocation of Bax to the mitochondria and release of cytochrome c induced by palmitate treatment. Furthermore, EPA, but not AA prevented the loss of mitochondrial cardiolipin due to apoptosis. These results suggest that EPA supplementation is able to protect cardiomyocytes against palmitate-induced apoptosis via an implication of different mitochondrial elements, possibly through its elongation to DPA, which is very efficient in cardiomyocytes.     

Temperature affects the limitation of Daphnia magna by eicosapentaenoic acid,and the fatty acid composition of body tissue and eggs

1. Poikilothermic animals incorporate more polyunsaturated fatty acids (PUFAs) into their cellular membranes as temperature declines, suggesting an increased sensitivity to PUFA limitation in cool conditions. To test this we raised Daphnia magna at different temperatures and investigated the effect of varying dietary PUFA on life history parameters (i.e. growth, reproduction) and the PUFA composition of body tissue and eggs. 2. Upon a PUFA‐rich diet (Cryptomonas sp.) females showed higher concentrations of several ω3 PUFAs in their body tissue at 15 °C than at 20 °C and 25 °C, indicating a greater structural requirement for ω3 PUFAs at low temperature. Their eggs had an equal but higher concentration of ω3 PUFAs than their body tissue. 3. In a life history experiment at 15 and 20 °C we supplemented a diet of a PUFA‐free cyanobacterium with the ω3 PUFA eicosapentaenoic acid (EPA). The growth of D. magna was more strongly EPA limited at low temperature. A greater requirement for structural EPA at 15 °C was indicated by a steeper increase in somatic EPA content with dietary EPA compared to 20 °C. 4. At 20 °C the development of eggs to successful hatching was high when EPA was supplied to the mothers. At 15 °C the hatching success was generally poor, despite of a higher maternal provision of EPA to eggs, compared to that at 20 °C, suggesting that EPA alone was insufficient for proper neonatal development at the low temperature. The growth of offspring from mothers raised at 20 °C without EPA supplementation was very low, indicating that the negative effects of EPA deficiency can be carried on to the next generation. 5. The fatty acid composition of Daphnia sp. in published field studies shows increasing proportions of saturated fatty acids with increasing environmental temperature, whereas ω3 PUFAs and EPA show no clear pattern, suggesting that variations in dietary PUFA may mask temperature‐dependent adjustments in ω3 PUFA concentrations of cladocerans in nature.     

Cultivation of Microorganisms in the Cultural Medium Made from Squid Internal Organs and Accumulation of Polyunsaturated Fatty Acids in the Cells

The disposal and more efficient utilization of marine wastes is becoming increasingly serious. A culture media for microorganisms has been prepared from squid internal organs that are rich in polyunsaturated fatty acids (PUFAs). Both freshwater and marine bacteria grew well in this medium and some bacteria accumulated PUFAs in their lipids, suggesting uptake of exogenous PUFAs. Higher PUFA accumulations were observed in Escherichia coli mutant cells defective either in unsaturated fatty acid biosynthesis or fatty acid degradation, or both, compared to those without these mutations. Therefore, PUFA accumulation in cells can be improved by genetic modification of fatty acid metabolism in the bacteria. Squid internal organs would be a good source of medium, not only for marine bacteria but also for freshwater bacteria, and that this process may be advantageous to make efficient use of the fishery wastes and to produce PUFA-containing microbial cells and lipids.     

Membrane fluidity changes are associated with the antiarrhythmic effects of docosahexaenoic acid in adult rat cardiomyocytes

Previous studies using neonatal rat cardiomyocytes have reported antiarrhythmic effects of long-chain polyunsaturated fatty acids (PUFAs). In this study, we examined the effects of the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) on the spontaneous contractile activity and membrane fluidity of adult rat ventricular myocytes. Cardiomyocytes were induced to contract spontaneously by continuous superfusion of a solution containing the arrhythmogenic agents isoproterenol (a beta-adrenergic receptor agonist) or lysophosphatidylcholine. The percentage of cardiomyocytes displaying spontaneous contractions induced by isoproterenol when pretreated with the saturated fatty acid docosanoic acid was 48.1 +/- 7.7%; the percentage for cardiomyocytes pretreated with DHA was 7.1 +/- 2.4% (P < 0.01). DHA significantly prevented lysophosphatidylcholine-induced spontaneous contractions (17.7 +/- 6.5%) compared with treatment with the saturated fatty acid stearic acid (78.0 +/- 7.3%, P < 0.01). The membrane fluidizing agent benzyl alcohol also significantly prevented spontaneous contractions in cardiomyocytes. Membrane fluidity was determined by steady-state fluorescence anisotropy (r(ss)) using the fluorescent probe N-((4-(6-phenyl-1,3,5-hexatrienyl)phenyl)propyl) trimethyl-ammonium p-toluene-sulfonate (TMAP-DPH). DHA and benzyl alcohol dose-dependently decreased the r(ss); however, saturated fatty acids were without effect. These results suggest that the antiarrhythmic mechanisms of the n-3 PUFAs such as DHA may involve changes in membrane fluidity.     

Fatty acid compositions of Collembola: unusually high proportions of C20 polyunsaturated fatty acids in a terrestrial invertebrate

To examine the C(20) polyunsaturated fatty acid (PUFA) compositions of Collembola, we raised five species of Collembola on yeast diets, and then quantified body mass, neutral lipid fatty acid (NLFA) and phospholipid fatty acid (PLFA) compositions. PLFA content was always less than 5% of dry weight, but NLFA content varied from 5.9% to 29.6% of dry weight, depending upon species. Combined C(20) PUFA proportions of up to 9.2% and 48% were observed in the NLFA and PLFA fractions, respectively, resulting in total C(20) PUFA proportions of up to 19.4% of the total fatty acid compositions of Collembola. C(20) PUFAs were also detected in Collembola specimens from a deciduous woodland at proportions up to 29.7% of the total fatty acid composition. Terrestrial invertebrates generally contain <4% and <22% C(20) PUFAs in PLFAs and NLFAs, respectively; therefore, these results demonstrate that Collembola often possess the highest proportions of C(20) PUFAs yet observed in terrestrial invertebrates. The biochemical reasons for such high C(20) PUFA proportions, which were biosynthesised by the Collembola since these components were absent from the yeast diets, remain unclear. The distinctive fatty acid compositions of Collembola may be useful in soil food web studies utilising fatty acids as biomarkers of trophic behaviour.     

Fat-1基因在n-3多不饱和脂肪酸功能研究中的应用

n-3多不饱和脂肪酸是机体脂肪酸成分之一,维持体内合理的n-3多不饱和脂肪酸比例具有重要的生理意义。但n-3多不饱和脂肪酸在大多数动物体内不能合成,只能从食物中补充。fat-1基因的出现改变了这一现状,它可以将多不饱和脂肪酸从n-6形式转化为n-3形式。文章综述了n-3多不饱和脂肪酸的功能,并介绍了fat-1基因的功能及转fat-1基因动物在n-3多不饱和脂肪酸功能研究上的应用。     

Noninvasive analyses of polyunsaturated fatty acids in human oral mucosa in vivo by Fourier-transform infrared spectroscopy

The aim of this study was to develop a noninvasive method to observe polyunsaturated fatty acids (PUFAs) behavior in the human body using Fourier transform infrared spectroscopy. For the noninvasive measurement of human oral mucosa, we have used infrared spectroscopy with a suitable attachment for an in vivo attenuated total reflectance system. The fatty acid contents in the tissues were determined by gas-chromatography mass-spectrometry after methylation. The alkene C-H stretching vibrations of unsaturated fatty acids in dietary oils showed infrared absorption bands with various peak positions and intensities at around 3010 cm(-1) depending on the extent of unsaturation and their species. The diurnal fluctuation of the alkene peak position of oral mucosa suggested that the contents of PUFAs were increased gradually in the early afternoon, and these data were supported by the direct determination of fatty acid species in oral mucosa where the relative increase of arachidonic and docosahexaenoic acids was observed in the early afternoon. This diurnal change of alkene peak position resembled the pattern of a "lipid factor" change calculated with the factor analysis applied to the overall infrared spectrum. We could monitor the diurnal fluctuations of PUFA contents of human oral mucosa noninvasively using a reagent-free infrared analysis system. The measurement of alkene and methylene infrared bands may provide a useful tool for detecting changes in PUFA balance in the human body.     

Differential induction of electrophile-responsive element-regulated genes by n-3 and n-6 polyunsaturated fatty acids

In this study the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid appear to be effective inducers of electrophile-responsive element (EpRE) regulated genes, whereas the n-6 PUFA arachidonic acid is not. These n-3 PUFAs need to be oxidized to induce EpRE-regulated gene expression, as the antioxidant vitamin E can partially inhibit the PUFA induced dose-dependent effect. Results were obtained using a reporter gene assay, real-time RT-PCR and enzyme activity assays. The induction of EpRE-regulated phase II genes by n-3 PUFAs may be a major pathway by which n-3 PUFAs, in contrast to n-6 PUFAs, are chemopreventive and anticarcinogenic.     

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

We have recently identified a neuroprotective role for omega-3 polyunsaturated fatty acids (n-3 PUFAs) in a toxin-induced mouse model of Parkinson's disease (PD). Combined with epidemiological data, these observations suggest that low n-3 PUFA intake is a modifiable environmental risk factor for PD. In order to strengthen these preclinical findings as prerequisite to clinical trials, we further investigated the neuroprotective role of n-3 PUFAs in Fat-1 mice, a transgenic model expressing an n-3 fatty acid desaturase converting n-6 PUFAs into n-3 PUFAs. Here, we report that the expression of the fat-1 transgene increased cortical n-3:n-6 PUFA ratio (+28%), but to a lesser extent than dietary supplementation (92%). Such a limited endogenous production of n-3 PUFAs in the Fat-1 mouse was insufficient to confer neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity as assessed by dopamine levels, tyrosine hydroxylase (TH)-positive neurons and fibers, as well as nigral Nurr1 and dopamine transporter (DAT) mRNA expression. Nevertheless, higher cortical docosahexaenoic acid (DHA) concentrations were positively correlated with markers of nigral dopaminergic neurons such as the number of TH-positive cells, in addition to Nurr1 and DAT mRNA levels. These associations are consistent with the protective role of DHA in a mouse model of PD. Taken together, these data suggest that dietary intake of a preformed DHA supplement is more effective in reaching the brain and achieving neuroprotection in an animal model of PD.     

Incorporation and modification of dietary fatty acids in gill polar lipids by two bivalve species Crassostrea gigas and Ruditapes philippinarum

Two bivalve species Crassostrea gigas and Ruditapes philippinarum were fed eight weeks with three mono-specific algae diets: T-Isochrysis galbana, Tetraselmis suecica, Chaetoceros calcitrans, selected on the basis of their polyunsaturated fatty acid (PUFA) composition. The incorporation and the modification of dietary fatty acids in C. gigas and R. philippinarum gill lipids were analysed and compared. Essential PUFA (20:4n-6, 20:5n-3 and 22:6n-3) and non-methylene interrupted PUFAs (known to be synthesised from monounsaturated precursors) contents of gill polar lipid of both species were greatly influenced by the dietary conditioning. Interestingly, oysters and clams responded differentially to the mono-specific diets. Oysters maintained higher 20:5n-3 level and higher 22:2j/22:i and n-7/n-9 ratio in gill polar lipids than clams. To better discriminate dietary and species influences on the fatty acid composition, a Principal Component Analysis followed by a MANOVA on the two most explicative components was performed. These statistical analyses showed that difference in fatty acid compositions attributable to species were just as significant as the diet inputs. The differences of gill fatty acid compositions between oysters and clams are speculated to result of an intrinsic species characteristic and perhaps of a group characteristic: Fillibranch vs. Eulamellibranch.     

Long-chain polyunsaturated fatty acids in breast milk in La Plata, Argentina: relationship with maternal nutritional status

Milk fat is the major source of energy for breastfed infants; it also supplies polyunsaturated fatty acids (PUFAs) essential for the development of brain, retina, and other organs. Maternal nutritional status is critical for the newborn, and little information exists regarding the PUFA status of vulnerable populations living in Southern regions. We studied the relationship between maternal nourishment and milk fatty acid composition. Mother nutritional status (normal, overweight or obese) was estimated on the body mass index. Milk protein, total lipid, and fatty acid composition were determined. Milk protein was not affected by mother's nutritional status. In obese mothers an increase in lipid content, linoleic acid, total n-6 and total PUFAs was observed comparing to the other groups. Disregarding the nutritional status, the ratio n-6/n-3 fatty acids was very high and the 22:6n-3 content was very low, when compared with those of mothers from other countries. This finding led us to urge Public Health officers to promote changes in the dietary habits of nursing women.     

Specific polyunsaturated fatty acids drive TRPV-dependent sensory signaling in vivo

A variety of lipid and lipid-derived molecules can modulate TRP cation channel activity, but the identity of the lipids that affect TRP channel function in vivo is unknown. Here, we use genetic and behavioral analysis in the nematode C. elegans to implicate a subset of 20-carbon polyunsaturated fatty acids (PUFAs) in TRPV channel-dependent olfactory and nociceptive behaviors. Olfactory and nociceptive TRPV signaling are sustained by overlapping but nonidentical sets of 20-carbon PUFAs including eicosapentaenoic acid (EPA) and arachidonic acid (AA). PUFAs act upstream of TRPV family channels in sensory transduction. Short-term dietary supplementation with PUFAs can rescue PUFA biosynthetic mutants, and exogenous PUFAs elicit rapid TRPV-dependent calcium transients in sensory neurons, bypassing the normal requirement for PUFA synthesis. These results suggest that a subset of PUFAs with omega-3 and omega-6 acyl groups act as endogenous modulators of TRPV signal transduction.     

Construction of a series of intermediates in the β-oxidation pathway from THA to EPA via DHA in free acid form

β-Oxidation of most fatty acids occurs in the mitochondria. However, β-oxidation for ω-3 polyunsaturated fatty acids (PUFAs) is distinct from abundant fatty acids and occurs in the peroxisomes. Since little is known about peroxisomal β-oxidation, here we report the synthesis of proposed intermediates of ω-3 PUFA β-oxidation steps in free fatty acid form having a conjugated double bond, a β-hydroxyl group, a β-olefin and a β-carbonyl group. These fatty acids can serve as authentic samples for biological experiments.     

Unusual medium-chain polyunsaturated fatty acids from the snow alga Chloromonas brevispina

The gas chromatography-mass spectrometry (GC-MS) method was used to identify unusual medium-chain polyunsaturated fatty acids (PUFAs) in the snow alga Chloromonas brevispina collected in 2006 from surface layers of a snow field with conspicuous green patches in Bohemian Forest (Czech Republic). PUFAs formed more than 75% total fatty acids. Among them, mass spectroscopy of picolinyl esters showed sizable proportions of medium-chain PUFA, e.g., 5,8,11-tetradecatrienoic and 6,9,12-pentadecatrienoic acids. The high relative content of PUFA indicates that PUFA are an important element ensuring cell survival. Our report appears to be the first to describe the presence of short- and medium-chain PUFAs in green psychrophilic algae of the genus Chloromonas.     

A modified <Emphasis Type="Italic">n</Emphasis>–3 fatty acid desaturase gene from <Emphasis Type="Italic">Caenorhabditis briggsae</Emphasis> produced high proportion of DHA and DPA in transgenic mice

The functions of polyunsaturated fatty acids (PUFAs) have been widely investigated. In mammals, levels of n-3 PUFAs are relatively low compared to those of n-6 PUFAs. Either a lack of n-3 PUFAs or an excess of n-6 PUFAs could potentially cause health problems in humans. Hence, methods to increase the amount of n-3 PUFAs in diet have been intensely sought. In this study, we demonstrated that the n-3 fatty acid desaturase gene (sFat-1) synthesized from revised and optimized codons based on roundworm Caenorhabditis briggsae genomic gene for enhanced expression in mammals was successfully expressed in Chinese hamster ovary (CHO) cells and significantly elevated cellular n-3 PUFA contents. We generated sFat-1 transgenic mice by introducing mammal expression vector DNAs containing the sFat-1 gene into regular mice through the method of microinjection. Fatty acid compositions were then altered and the levels of docosahexaenoic acid (DHA, 22:6n-3) and docosapentaenoic acid (DPA, 22:5n-3) were greatly increased in these transgenic mice. Various types of tissues in the transgenic mice produced many types of n-3 PUFAs, such as alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), DPA, and DHA, for example, muscle tissues of the transgenic mice contained 12.2% DHA, 2.0% DPA, and 23.1% total n-3 PUFAs. These research results demonstrated that the synthesized sFat-1 gene with modified and optimized codons from C. briggsae possess functional activity and greater capability of producing n-3 PUFAs, especially DHA and DPA, in transgenic mice.     

Gut bacteria profiles of Mus musculus at the phylum and family levels are influenced by saturation of dietary fatty acids

BackgroundMammalian gut microbiota have been implicated in a variety of functions including the breakdown of ingested nutrients, the regulation of energy intake and storage, the control of immune system development and activity, and the synthesis of novel chemicals. Previous studies have shown that feeding mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce the ratio of Bacteroidetes-to-Firmicutes, while feeding hosts a fat-restricted diet increases this ratio. However, few studies have investigated the differential effects of fatty acid type on gut bacterial profile.MethodsOver a 14-week period, Mus musculus were fed a diet rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), or saturated fatty acids (SFAs). Fecal pellets were collected before and after the treatment period from 12 randomly selected mice (4 per treatment group). Bacterial DNA was extracted from the pellets and characterized by analysis of the hypervariable V3 region of the 16S rRNA. Nominal logistic regression models were used to assess shifts in microbial profile at the phylum and family levels in response to diet.ResultsA significant decrease in the proportion of phylum Bacteroidetes species was observed for mice fed any of the three diets over time. However, the SFA-rich diet group showed a significantly greater decrease in Bacteroidetes proportion (?28%) than did either the n-3 PUFA group (?10%) or the n-6 PUFA group (?12%). At the family level, a significant decrease in proportion of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet, and a significant decrease in proportion of Lachnospiraceae was observed for mice fed the SFA-rich diet. There was no significant effect of diet type on body mass change.ConclusionOur results indicate that SFAs have stronger effects than PUFAs in shifting gut microbiota profiles toward those typical of obese individuals, and that dietary fatty acid saturation influences shifts in gut microbiota independently of changes in body mass.     

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study

BackgroundWhether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.ConclusionsThese large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.     

Project DyAdd: Fatty acids and cognition in adults with dyslexia, ADHD, or both

Both attention deficit hyperactivity disorder (ADHD) and dyslexia are suggested to co-occur with altered fatty acid (FA) metabolism, but it is unknown how FAs are associated with the cognitive domains that characterize these disorders. In the project DyAdd, we investigated the associations between FAs in serum phospholipids and phonological processing, reading, spelling, arithmetic, executive functions, and attention. Healthy controls (n=36), adults with ADHD (n=26), dyslexia (n=36), or both (n=9) were included in the study. FAs included saturated, monounsaturated, total polyunsaturated, n-3, and n-6 FAs, together with n-6/n-3, AA/EPA, and LA/ALA ratios. When all the study subjects were included in the analyses, especially polyunsaturated FAs (PUFAs) were positively associated with cognition, but reading was least associated with FAs. These associations were modulated by gender, intelligence, n-3 PUFA intake, and group. Accordingly, within the ADHD group, only few associations emerged with PUFAs, n-6 PUFAs, and cognitive domains, whereas in the dyslexia group the more prevalent associations appeared with PUFAs and n-3 PUFAs.     

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA:n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations.