Families Of Polyunsaturated Fatty Acids Research Articles

Alternative fatty acid desaturation pathways revealed by deep profiling of total fatty acids in RAW 264.7 cell line

In-depth structural characterization of lipids provides a new means to investigate lipid metabolism. In this study, we have conducted deep profiling of total fatty acids (FAs) from RAW 264.7 macrophages by utilizing charge-tagging Paternò-Büchi derivatization of carbon-carbon double bond (C=C) and reversed-phase liquid chromatography-tandem mass spectrometry. A series of FAs exhibiting unusual site(s) of unsaturation was unearthed, with their identities being confirmed by observing anticipated compositional alterations upon desaturase inhibition. The data reveal that FADS2 Δ 6-desaturation can generate n-11 C=C in the odd-chain monounsaturated fatty acids (MUFAs) as well as n-10 and n-12 families of even-chain MUFAs. SCD1 Δ 9-desaturation yields n-6, n-8, and n-10 of odd-chain MUFAs, as well as n-5, n-7, and n-9 families of even-chain MUFAs. Besides n-3 and n-6 families of polyunsaturated fatty acids (PUFAs), the presence of n-7 and n-9 families of PUFAs indicates that the n-7 and n-9 isomers of FA 18:1 can be utilized as substrates for further desaturation and elongation. The n-7 and n-9 families of PUFAs identified in RAW 264.7 macrophages are noteworthy because their C=C modifications are achieved exclusively via de novo lipogenesis. Our discovery outlines the metabolic plasticity in fatty acid desaturation which constitutes an unexplored rewiring in RAW264.7 macrophages.

Analysis of epigenetic mediators for the effect of Polyunsaturated fatty acids Omega6/3 ratio on cognitive function and progression to dementia

AbstractBackgroundPrevious research reported the association between circulating Omega‐3 polyunsaturated fatty acids (PUFA) in blood and the risk of dementia and Alzheimer’s disease (AD). However, a large intervention study supplementing Omega‐3 reported that this supplementation has only a marginal effect on improvement of cognitive performance after the supplementation. Since PUFA metabolism shared the processing enzymes, we explored whether the relationship between two main families of PUFA, i.e., Omega‐3 and Omega‐6, might associate with cognitive performance. Hence, we observed that the ratio Omega‐6/Omega‐3 in blood is associated with cognitive decline and dementia. To follow up on this finding, we sought to explore whether modulation of immune response and inflammation may underlie these effects.MethodThree independent cohort were used for this study: i) the observational memory‐clinic‐based cohort DELCODE (n = 1036); ii) the primary care‐derived cohort AgeCoDe (n = 1252); iii) the Multidomain Alzheimer Preventive Trial (MAPT study) cohort (n = 1679). Omega‐3 and PUFA levels were quantified specifically in plasma from each cohort. COX regressions and linear mixed models were applied to evaluate PUFA ratio effect on cognitive performance and progression to dementia. Genomic and epigenomic modulators for the observed effects were further explored using the previously published tool (MetaMeth). Results were confirmed using our pipeline for epigenome‐wide association study (EWAS).ResultOmega‐6/Omega‐3 ratio is associated with cognitive performance and risk of progressing to AD in DELCODE and AgeCoDe. In MAPT, the improvement of this ratio is associated with improvement on cognitive performance. Moreover, levels of Omega‐3 in blood modulate methylation of genes coding for key enzymes of PUFA metabolism. Our data showed that the biological effect for some genetic susceptibility signals for AD is mediated by changes in DNA methylation, including immune‐related genes like MS4A and TREM2.ConclusionOur data suggests that balance between PUFA is relevant on cognitive decline and dementia. In addition, the genetic effect of risk variants located at the AD risk loci containing the MS4A gene cluster and TREM2 are mediated by changes in methylation. To provide a connection between PUFA and neuroinflammation in the context of AD, we are currently exploring the effect of PUFA levels on DNA methylation at MS4A and TREM2 loci.

Abstract 240: Bioactive Lipids In Circulation: Biomarker Of Ageing?

Blood transports cells and nutrients. However, it is less known that the major plasma compound is the lipid family in the broad sense. Among these lipids, cholesterol, triglyceride but also the family of polyunsaturated fatty acids (PUFAs) and their metabolites. These lipid mediators are involved in several chronic, inflammatory diseases such as rheumatoid arthritis. But, ageing is associated with chronic inflammation and affects almost 20% of the world’s population. Thus, it is by far the most important population before cardiovascular disease and cancer. Using mass spectrometry analyses, we evaluated the levels of different classes of lipid mediators from healthy young and elderly donors (single donor apheresis). Our data showed a significant decrease of lysophosphatidic acid species‘s expression, modulation of the 5-lipoxygenase product’s, as well as lipid mediators derived from PUFA oxidation. Their effect on blood vessel and circulating cells influenced their function. Indeed, lipid mediator intake is involved in transfusion reactions, and we observed an activation of blood cells, especially platelet, with significant increase of p-selectin. These data highlighted the importance of lipid mediator level in a context of transfusion and ageing of blood donor independently of the storage time of single donor apheresis. They can serve as biomarker of ageing.

Izmenjen profil masnih kiselina eritrocita pacijenata sa amiotrofičnom lateralnom sklerozom - korelacija sa trajanjem bolesti

Background: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed als patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration. Methods: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed als patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers. Results: Significantly higher levels of palmitic acid and total saturated FAs were detected in als patients. In als patients, total monounsaturated FA, palmitoleic, vaccenic, and oleic acid were also significantly increased. The levels of eicosapentaenoic acid, docosapentaenoic acid, total polyunsaturated FA (PUFA) and n-6 PUFA were significantly lower in als patients. Additionally, a-linolenic acid, the precursor of the n-3 PUFA family, was not detected in als patients. We found no significant correlation between the ALSFRS-R score and the abundance of individual FAs analysed. A moderate negative correlation was found between disease duration and DHA level, and a positive correlation was detected with MUFA. Conclusion: Experimental evidence presented may contribute to shaping a beneficial nutritional intervention.

Fish Oil - Omega-3 Exerts Protective Effect in Oxidative Stress and Liver Dysfunctions Resulting from Experimental Sepsis

Sepsis is a severe global health problem, with high morbidity and mortality. In sepsis, one of the main affected organs is the liver. Hepatic alterations characterize a negative prognostic. Omega-3 fatty acids (ω3), eicosapentaenoic acid, and docosahexaenoic acid, are part of the main families of polyunsaturated fatty acids. ω3 has been used in studies as sepsis treatment and as a treatment for non-alcoholic liver disease. We aimed to evaluate the effects of treatment with fish oil (FO) rich in ω3 on liver changes and damage resulting from experimental sepsis. A model of severe sepsis in Wistar rats was used. Oxidative stress in the liver tissue was evaluated by means of tests of thiobarbituric acid reactive substances, 2,7-dihydrodichlorofluorescein diacetate , catalase, and glutathione peroxidase, in the serum TBARS, DCF, thiols and, to assess liver dysfunction, alanine aminotransferase and aspartate aminotransferase. Hepatic tissue damage was evaluated using H&E histology. In assessments of oxidative stress in liver tissue, a protective effect was observed in the tests of TBARS, DCF, CAT, and GPx, when compared the sepsis versus sepsis+ω3 groups. Regarding the oxidative stress in serum, a protective effect of treatment with ω3 was observed in the TBARS, DCF, and thiols assays, in the comparison between the sepsis and sepsis+ω3 groups. ω3 had also a beneficial effect on biochemical parameters in serum in the analysis of ALT, creatinine, urea, and lactate, observed in the comparison between the sepsis and sepsis+ω3 groups. The results suggest ω3 as a liver protector during sepsis with an antioxidant effect, alleviating injuries and dysfunctions.

Polyunsaturated Fatty Acids: Impact on Health and Disease Status


 
 
 Over the last decades, the polyunsaturated fatty acids (PUFAs) have been largely explored not only for their nutritional value but also for the numerous biological functions and therapeutic effects. The serum and erythrocyte levels of PUFAs depend on the genetic control of metabolism as well as the dietary intake and are considered to reflect the health and disease status of an individual. Two families of PUFAs, omega-3 (n-3) and omega-6 (n-6), have gained much attention because of their involvement in the production of bioactive lipid mediators and therefore, a balanced omega-6/omega-3 ratio is crucial in maintaining the overall health of an individual. Omega-3 PUFAs, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have been shown to exert beneficial effects, possibly due to their lipid-lowering, anti-inflammatory, anti-hypertensive and cardioprotective effects, whereas omega-6 fatty acids such as arachidonic acid (ARA, 20:4n-6) exhibit the opposite properties. Even though, numerous epidemiological studies and clinical interventions have clearly established the effectiveness of omega-3 PUFAs in various pathological conditions including dyslipidemia, obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases, some controversies do exist about the beneficial effects of omega-3 PUFAs and need to be clarified. Larger clinical trials with extended follow-up periods are required along with a careful dose selection, in order to confirm the clinical significance and efficacy of omega-3 PUFAs as therapeutic agents.
 
 

Food for mood: Relevance of nutritional Omega-3 fatty acids for depression and anxiety

Polyunsaturated fatty acids (PUFAs) are essential fatty acids which are provided to the body through the diet. The brain is one of the richest organs in the body and has a high need in PUFAs. There are 2 main families of PUFAs, n-3 (or omega 3) and n-6 (or omega6). While it is quite easy to find n-6 PUFAs in westernized diets, the need in n-3 PUFAs is poorly reached, leading to decreased level of docosahexaenoic acid (DHA) in the brain. In humans, poor levels of blood n-3 PUFAs and brain DHA are associated to a higher prevalence of cognitive disorders and depression. However, the mechanisms underlying the effect of DHA on brain functions are poorly understood. Using mice models of n-3 PUFAs dietary deficiency or supplementation, we revealed that in the brain, DHA regulate neuroinflammatory pathways, in particular through its effect on microglia, the main innate immune system cell in the brain. In addition, n-3 PUFAs are key actors of ndocannabinoid- dependent synaptic plasticity. While neuroinflammation and eCB-dependent synaptic plasticity are crucial to cognition and emotional behaviour alterations, our results bring to the clinical scene the importance of controlling dietary n-3 PUFAs to protect the brain from the adverse effect of stres or inflammation. Altogether, our work brings a better comprehension of how dietary n-3 PUFAs participate to brain physiology and protect from the development of mood and cognitive disorders. It opens new avenues for the use of these lipids in the protection and treatment of brain diseases.DisclosureNo significant relationships.

Metabolomic analysis to elucidate the change of the n-3 polyunsaturated fatty acids in senescent osteoblasts.

Senile osteoporosis is a major public health concern, and yet, effective treatment methods do not exist. Herein, we used metabolomics to analyze the change of n-3 polyunsaturated fatty acids (PUFA) in senescent osteoblasts. We found that with an increase in the number of passages, the osteoblasts proliferative ability, alkaline phosphatase activity, and expression levels of bone metabolism genes decreased, the expression levels of aging-related genes increased, the damage caused by oxidative stress became more severe. Furthermore, levels of n-3 PUFA family members were downregulated in passage 10 than in passage 3 osteoblasts. These findings indicated that multiple passages led to more severe oxidative stress damage in senescent osteoblasts, which could be related to a decrease in n-3 PUFA levels. We believe that unsaturated fatty acid metabolism is a key factor involved in osteoblast senescence and that a proper dietary intake of n-3 PUFA may delay the occurrence senile osteoporosis.

Endocannabinoids and aging-Inflammation, neuroplasticity, mood and pain.

Aging is associated with changes in hormones, slowing of metabolism, diminished physiological processes, chronic inflammation and high exposure to oxidative stress factors, generally described as the biological cost of living. Lifestyle interventions of diet and exercise can improve the quality of life during aging and lower diet-related chronic disease. The endocannabinoid system (ECS) has important effects on systemic metabolism and physiological systems, including the central and peripheral nervous systems. Exercise can reduce the loss of muscle mass and improve strength, and increase the levels of endocannabinoids (eCB) in brain and blood. Although the ECS exerts controls on multiple systems throughout life it affords benefits to natural aging. The eCB are synthesized from polyunsaturated fatty acids (PUFA) and the primary ones are produced from arachidonic acid (n-6 PUFA) and others from the n-3 PUFA, namely eicosapentaenoic and docosahexaenoic acids. The eCB ligands bind to their receptors, CB1 and CB2, with effects on appetite stimulation, metabolism, immune functions, and brain physiology and neuroplasticity. Dietary families of PUFA are a primary factor that can influence the types and levels of eCB and as a consequence, the downstream actions when the ligands bind to their receptors. Furthermore, the association of eCB with the synthesis of oxylipins (OxL) is a connection between the physiological actions of eCB and the lipid derived immunological OxL mediators of inflammation. OxL are ubiquitous and influence neuroinflammation and inflammatory processes. The emerging actions of eCB on neuroplasticity, well-being and pain are important to aging. Herein, we present information about the ECS and its components, how exercise and diet affects specific eCB, their role in neuroplasticity, neuroinflammation, pain, mood, and relationship to OxL. Poor nutrition status and low nutrient intakes observed with many elderly are reasons to examine the role of dietary PUFA actions on the ECS to improve health.

Oxidation of polyunsaturated fatty acids to produce lipid mediators.

The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or specialized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 (n-6) or the omega-3 (n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C20 fatty acids, and include prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family produce numerous other metabolites. In plants, the lipoxygenase pathway from C18 polyunsaturated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions. Related oxylipins are produced by non-enzymic means (isoprostanes), while fatty acid esters of hydroxy fatty acids (FAHFA) are now being considered together with the oxylipins from a functional perspective. In all kingdoms of life, oxylipins usually act as lipid mediators through specific receptors, have short half-lives and have functions in innumerable biological contexts.

Supplementation with omega-3 fatty acids potentiates oxidative stress in human airway epithelial cells exposed to ozone

BackgroundDietary intake of the omega-3 family of polyunsaturated fatty acids (ω-3 FA) is associated with anti-inflammatory effects. However, unsaturated fatty acids are susceptible to oxidation, which produces pro-inflammatory mediators. Ozone (O3) is a tropospheric pollutant that reacts rapidly with unsaturated fatty acids to produce electrophilic and oxidative mediators of inflammation. ObjectiveDetermine whether supplementation with ω-3 FA alters O3-induced oxidative stress in human airway epithelial cells (HAEC). Methods16-HBE cells expressing a genetically encoded sensor of the reduced to oxidized glutathione ratio (GSH/GSSG, EGSH) were supplemented with saturated, monounsaturated, or ω-3 FA prior to exposure to 0, 0.08, 0.1, or 0.3 ppm O3. Lipid peroxidation was measured in cellular lipid extracts and intact cells following O3 exposure. ResultsRelative to cells incubated with the saturated or monounsaturated fatty acids, cells supplemented with ω-3 FA containing 5 or 6 double bonds showed a marked increase in EGSH during exposure to O3 concentrations as low as 0.08 ppm. Consistent with this finding, the concentration of lipid hydroperoxides produced following O3 exposure was significantly elevated in ω-3 FA supplemented cells. DiscussionSupplementation with polyunsaturated ω-3 FA potentiates oxidative responses, as indicated by EGSH, in HAEC exposed to environmentally relevant concentrations of O3. This effect is mediated by the increased formation of lipid hydroperoxides produced by the reaction of O3 with polyunsaturated fatty acids. Given the inflammatory activity of lipid hydroperoxides, these findings have implications for the potential role of ω-3 FA in increasing human susceptibility to the adverse health effects of O3 exposure.

Effects of Omega-3 Fatty Acids on Immune Cells.

Alterations on the immune system caused by omega-3 fatty acids have been described for 30 years. This family of polyunsaturated fatty acids exerts major alterations on the activation of cells from both the innate and the adaptive immune system, although the mechanisms for such regulation are diverse. First, as a constitutive part of the cellular membrane, omega-3 fatty acids can regulate cellular membrane properties, such as membrane fluidity or complex assembly in lipid rafts. In recent years, however, a new role for omega-3 fatty acids and their derivatives as signaling molecules has emerged. In this review, we describe the latest findings describing the effects of omega-3 fatty acids on different cells from the immune system and their possible molecular mechanisms.

Fatty Acids of the Medusae Aureliaaurita (Linnaeus, 1758) and Rhopilemaesculentum (Kishinouye, 1891): The Presence of Families of Polyenoic Acids with 24 and 26 Carbon Atoms

It was found that lipids of scyphoid jellyfishes of the Sea of Japan, Aurelia aurita (Linnaeus, 1758) and Rhopilema esculentum (Kishinouye, 1891) contain, along with the common fatty acids (FAs) that are characteristic of marine organisms, notable concentrations of polyunsaturated fatty acids (PUFAs) with 24 and 26 carbon atoms. The main PUFAs in A. aurita and Rh. esculentum were 20:5(n–3), 22:6(n–3), 24:6(n–3), and 22:5(n–3). In addition, it was found for the first time that Rh. esculentum contains 1.6% C26 PUFAs: C26:7(n–3), C26:6(n–3), and C26:5(n–3). In spite of similar PUFA levels in A. aurita and Rh. esculentum (65.95 and 58.79%, respectively), the ratio of the FA (n–3)/(n–6) families was in A. aurita 7 times higher than in Rh. esculentum. Saturated acids (26.57% in A. aurita and 31.75% in Rh. esculentum) were represented by palmitic and stearic acids. The level of monounsaturated FAs, including C16:1 and C18:1 isomers, was low and did not exceed 10% in both species. The presence of unusual families of PUFAs with 24 and 26 carbon atoms and the difference in the contents of FAs (n–3) and (n–6) in species that live under similar conditions is of great interest.

Protection against Oxidation of Omega-3 Fatty Acids with Natural Antioxidants in Clove (Szygium aromaticum) Water Extracts during Storage of Sun dried Sardines (Ratrineobola argentea)

Omega-3 fatty acids are a family of polyunsaturated fatty acids (PUFAs) with beneficial health effects to humans if consumed in required amounts. Fatty fish species are known to be rich in marine-based omega-3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and docosapentaenoic acid (DPA, C22:5n-3). Sardines (Rastrineobola argentea) from Lake Victoria are a good source of health promoting omega-3 fatty acids. Open sun drying is a common and traditional sardine processing and preservation method. Due to their chemical instability omega-3 fatty acids in sun dried sardines are prone to lipid oxidation during processing and subsequent storage. This study investigated the use of clove (Syzygium aromaticum) water extracts as natural antioxidants to protect omega-3 fatty acids against oxidative damage during storage of sun dried sardines. Lipid oxidation was assessed by peroxide value, volatile secondary oxidation products and fatty acid profiles. The antioxidant capacity of extracts was evaluated by total phenolic content, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and iron (Fe2+) chelating ability. Clove extracts resulted into significantly higher retention of total PUFAs, DHA, EPA and DPA at the end of 30 days storage period and lower concentrations of secondary lipid oxidation products. This is an evidence of their enhanced oxidative stability in the real food system due to presence of natural clove antioxidants.

Gamma linolenic acid regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DEN induced hepatocellular carcinoma.

IntroductionHepatocellular carcinoma (HCC) is one of the known major health problems across the globe, and is sixth ranked among all cancer, due to its high mortality rate. Polyunsaturated fatty acids (PUFAs) play an important role in the formation of a cell membrane, along with the fluidity of the membrane and proteins. Gamma linolenic acid (GLA) is member of the ω-6 family of PUFAs and converts into the arachidonic acid via a series of elongation and desaturation reactions. The aim of the current investigation was to scrutinize the effect of GLA on mitochondrial mediated apoptosis and anti-inflammatory pathway against diethylnitrosamine (DEN) induced HCC.Materials and methodsChemical carcinogenesis in Wistar rats was introduced by an intra-peritoneal dose of DEN (200 mg/kg). The rats received the various doses of GLA for 22 weeks. The progressions of serum biomarkers and histopathology components of hepatic tissue were used to access the prophylactic effects. The antioxidant parameters, cancer preventive agent status, and apoptosis mechanism were reviewed to scrutinize the possible mechanism.ResultsDose-dependent treatment of GLA significantly (P<−0.001) modulated the hepatic nodules, hepatic, body weight, antioxidant, and non-hepatic parameters. Curiously, the Real-time polymerase chain reaction (RT-PCR) and immunoblotting showed the GLA altered reduced the hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammsatory pathways.ConclusionOn the basis of the above results, we can conclude that the GLA exhibited a chemo-protective effect against DEN induced HCC that might be due to the altered hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammatory pathway, respectively.

Invited review: Roles of dietary n-3 fatty acids in performance, milk fat composition, and reproductive and immune systems in dairy cattle

Mammals can synthesize all of the fatty acids (FA) necessary for proper health and functioning with the exception of FA in the n-3 (omega-3) and n-6 (omega-6) families of polyunsaturated fatty acids (PUFA), which should be supplied in the diet. The PUFA are the predominant type of lipid in dairy cattle diets; however, common feedstuffs are rich in n-6 FA, whereas the supply of n-3 FA in the intensive dairy industry is mainly limited to flaxseed and fish oils. The n-3 FA are involved in many biological systems and processes, and therefore their dietary supplementation is of special interest in dairy cattle. Furthermore, because milk, milk products, and meat are among the most important and widely used components in traditional and modern human diets, enrichment of these food products with n-3 FA is of special importance. The purpose of this review is to provide a comprehensive description of different aspects and outcomes involved in dietary n-3 FA supplementation in dairy cattle. I provide an inclusive review of the effects of n-3 FA on milk and milk solids and the FA profile in milk fat upon feeding a variety of flaxseed products or fish oil. Selective uptake of n-3 FA has been demonstrated in the ovary compartments, as well as in bull sperm and in the unborn calf through the placenta. Incorporation of these unique FA into the reproductive system influences many processes and exerts some positive effects on fertility. In addition, beneficial effects of feeding n-3 FA on the reproductive system of females and males can be achieved with supplementation of α-linolenic acid from flaxseed or from eicosapentaenoic and docosahexaenoic acids from fish oil. This work provides a broad perspective and demonstrates the importance and potential of n-3 FA dietary supplementation in dairy cattle on the animal itself, as well as its secondary effects, which are associated with human nutrition and health.

Maternal intake of omega-3 and omega-6 polyunsaturated fatty acids during mid-pregnancy is inversely associated with linear growth

This study investigates relations of maternal N-3 and N-6 polyunsaturated fatty acids (PUFA) intake during pregnancy with offspring body mass index (BMI), height z-score and metabolic risk (fasting glucose, C-peptide, leptin, lipid profile) during peripuberty (8-14 years) among 236 mother-child pairs in Mexico. We used food frequency questionnaire data to quantify trimester-specific intake of N-3 alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); N-6 linoleic acid and arachidonic acid (AA); and N-6:N-3 (AA:EPA+DHA), which accounts for the fact that the two PUFA families have opposing effects on physiology. Next, we used multivariable linear regression models that accounted for maternal education and parity, and child's age, sex and pubertal status, to examine associations of PUFA intake with the offspring outcomes. In models where BMI z-score was the outcome, we also adjusted for height z-score. We found that higher second trimester intake of EPA, DHA and AA were associated with lower offspring BMI and height z-score. For example, each 1-s.d. increment in second trimester EPA intake corresponded with 0.25 (95% CI: 0.03, 0.47) z-scores lower BMI and 0.20 (0.05, 0.36) z-scores lower height. Accounting for height z-score in models where BMI z-score was the outcome attenuated estimates [e.g., EPA: -0.16 (-0.37, 0.05)], suggesting that this relationship was driven by slower linear growth rather than excess adiposity. Maternal PUFA intake was not associated with the offspring metabolic biomarkers. Our findings suggest that higher PUFA intake during mid-pregnancy is associated with lower attained height in offspring during peripuberty. Additional research is needed to elucidate mechanisms and to confirm findings in other populations.

Narrow-spectrum inhibitors targeting an alternative menaquinone biosynthetic pathway of Helicobacter pylori.

We aimed to identify narrow-spectrum natural compounds that specifically inhibit an alternative menaquinone (MK; vitamin K2) biosynthetic pathway (the futalosine pathway) of Helicobacter pylori. Culture broth samples of 6183 microbes were examined using the paper disc method with different combinations of 2 of the following 3 indicator microorganisms: Bacillus halodurans C-125 and Kitasatospora setae KM-6054(T), which have only the futalosine pathway of MK biosynthesis, and Bacillus subtilis H17, which has only the canonical MK biosynthetic pathway. Most of the active compounds isolated from culture broth samples were from the families of polyunsaturated fatty acids (PUFAs). Only one compound isolated from the culture broth of Streptomyces sp. K12-1112, siamycin I (a 21-residue lasso peptide antibiotic), targeted the futalosine pathway. The inhibitory activities of representative PUFAs and siamycin I against the growth of B.halodurans or K.setae were abrogated by supplementation with MK. Thereafter, the growth of H.pylori strains SS1 and TN2GF4 in broth cultures was dose-dependently suppressed by eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or siamycin I, and these inhibitory effects were reduced by supplementation with MK. Daily administration of EPA (100μM), DHA (100μM), or siamycin I (2.5μM) in drinking water reduced the H.pylori SS1 colonization in the gastric mucosa of C57BL/6 mice by 96%, 78%, and 68%, respectively. These data suggest that EPA, DHA, and siamycin I prevented H.pylori infection by inhibiting the futalosine pathway of MK biosynthesis.

Role of Omega-3 PUFAs in Neurobiological Health.

The importance of the essential, dietary-derived, polyunsaturated fatty acids (PUFAs) omega-6 and omega-3 to human health was first reported over 85 years ago. Subsequent research has revealed many beneficial effects of the omega-3 PUFAs in particular. This has been linked to their involvement in multiple biochemical functions, including synthesis of inflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. Through these pathways, the omega-3 PUFAs help modulate aspects of inflammation and immunity, cell growth and tissue repair. While a detailed understanding of the mechanisms involved in the role of omega-3 PUFAs to health in the central nervous system (CNS) is still to be elucidated, a role for both inflammatory modulation and a direct impact on neuronal membrane fluidity and receptor function is apparent. At least partially through these mechanisms, low omega-3 levels have been associated with CNS-linked disorders such as poor cognition, depression, anxiety disorders, poor anger control, attention deficit hyperactivity disorder (ADHD) and accelerated neurodegeneration in the elderly.Following a brief introduction to the history and chemistry of the omega-3 family of PUFAs, this chapter will provide an overview of the omega-3 fatty acids and how various members of this PUFA family influence central nervous system function leading towards either health or disease.

A review of recent evidence in human studies of n-3 and n-6 PUFA intake on cardiovascular disease, cancer, and depressive disorders: does the ratio really matter?

Polyunsaturated fatty acids (PUFAs) have been considered of great interest for human health due to their potential anti-inflammatory action that may protect from a number of chronic-degenerative diseases with an inflammatory pathogenesis. This review aimed to report the most updated evidence of both n-3 and n-6 PUFAs effect on cardiovascular disease, cancer, and depression in humans. Attention has been also paid to those studies exploring the effects of the ratio intake. Results from pooled analyses of human studies reported a general positive effect of n-3 PUFAs intake on all outcomes considered. In contrast, the role of n-6 PUFAs on human health needs to be better assessed in order to clearly identify which compound exerts beneficial/harmful effects. Only a limited number of clinical studies considered the n-3:n-6 PUFAs ratio, rather reporting contrasting results. A number of limitations when considering the ratio between these two families of PUFAs have risen.