Omega-3 and -6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines.

The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.

Antimicrobial and antibiofilm effects of essential fatty acids against clinically isolated vancomycin-resistant Enterococcus faecium.

Introduction: Enterococcus faecium is a leading cause of hospital-acquired infections, which has become a serious public health concern. The increasing incidence of vancomycin-resistant E. faecium (VRE-fm) raises an urgent need to find new antimicrobial agents as a complement to traditional antibiotics. The study aimed to evaluate the antimicrobial and antibiofilm activity of essential fatty acids (EFAs) against VRE-fm, and further explore the molecular mechanism of the antibiofilm activity of EFAs. Method: The microdilution broth method was used for antimicrobial susceptibility testing with traditional antibiotics and EFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA). The effect of EFAs on cell morphology of VRE-fm was investigated by scanning electron microscopy. The crystal violet method was used to evaluate the antibiofilm activities of EFAs against VRE-fm. Furthermore, the expression of biofilm-related genes (acm, atlA, esp, and sagA) of VRE-fm isolates under the action of GLA was analyzed using quantitative reverse transcription PCR (qRT-PCR) assay. Results: VRE-fm isolates were highly resistant to most traditional antibiotics, only highly susceptible to quinupristin-dalfopristin (90.0%), tigecycline (100%), and linezolid (100%). EPA, DHA, and GLA exhibited excellent antimicrobial activity. The MIC50/90 of EPA, DHA, and GLA were 0.5/1, 0.25/0.5, and 0.5/1 mM, respectively. SEM imaging showed that strain V27 adsorbed a large number of DHA molecules. Furthermore, all EFAs exhibited excellent inhibition and eradication activities against VRE-fm biofilms. The biofilm inhibition rates of EFAs ranged from 45.3% to 58.0%, and eradication rates ranged from 54.1% to 63.4%, against 6 VRE-fm isolates with moderate biofilm formation ability. GLA exhibited remarkable antibiofilm activity against VRE-fm isolates. The qRT-PCR analysis showed that GLA could significantly down-regulate the expression of the atlA gene (P < 0.01) of VRE-fm. Conclusion: DHA showed the strongest antibacterial activity, while GLA showed the strongest antibiofilm effect among the EFAs with antibacterial activity. Our novel findings indicate that the antibiofilm activity of GLA may be through down-regulating the atlA gene expression in VRE-fm. Therefore, DHA and GLA had the potential to be developed as therapeutic agents to treat infections related to multiple antimicrobial-resistant E. faecium.

Abomasal infusion of essential fatty acids and conjugated linoleic acid during late pregnancy and early lactation affects immunohematological and oxidative stress markers in dairy cows.

Oxidative stress and inflammation, as natural parts of metabolic adaptations during the transition from late gestation to early lactation, are critical indicators of dairy cows' metabolic health. This study was designed to investigate the effects of abomasal infusion of essential fatty acids (EFA), particularly α-linolenic acid, and conjugated linoleic acid (CLA) on plasma, erythrocyte, and liver markers of oxidative stress in dairy cows during the transition period. Rumen-cannulated German Holstein cows (n = 38) in their second lactation (11,101 ± 1,118 kg milk/305 d, mean ± standard deviation) were abomasally infused with one of the following treatments from d -63 antepartum until d 63 postpartum (PP): CTRL (n = 9; 76 g/d coconut oil); EFA (n = 9; 78 g/d linseed plus 4 g/d safflower oil); CLA (n = 10; isomers cis-9,trans-11 and trans-10,cis-12 CLA; 38 g/d); and EFA+CLA (n = 10; 120 g/d). Hematological parameters as well as markers of oxidative status were measured in plasma, erythrocytes, and liver before and after calving. Immunohematological parameters, including erythrocyte number, hematocrit, hemoglobin, mean corpuscular hemoglobin, leukocytes, and basophils, were affected by time, and their peak levels were observed on the day after calving. The oxidative stress markers glutathione peroxidase 1 and reactive oxygen metabolites in plasma and erythrocytes were both affected by time, exhibiting the highest levels on d 1 PP, whereas ß-carotene, retinol, and tocopherol were at their lowest levels at the same time. Immunohematological parameters were only marginally affected by fatty acid treatment in a time-dependent manner. As such, lymphocyte and atypical lymphocyte counts were both significantly highest in the groups that received EFA at d 1 PP. Moreover, EFA supplementation increased the mean corpuscular volume and showed a trend for induction of mean corpuscular hemoglobin compared with the CLA group during the transition period. The PP mean thrombocyte volume was higher in the EFA than in the CLA group (except for d 28) and both EFA and CLA reduced number of thrombocytes and thrombocrit at distinct time points. Hepatic mRNA abundance of markers related to oxidative status, including glutathione peroxidase (GPX-1) and catalase (CAT), was lower (P < 0.05) in EFA-treated than non-EFA-treated cows at d 28 PP. Dairy cows at the onset of lactation were characterized by induced markers of both oxidative stress and inflammation. Supplementing EFA and CLA had minor and time-dependent effects on markers of oxidative stress in plasma, erythrocytes, and liver. A comparison of EFA supplementation with CLA or CTRL showed higher immunohematological response at d 1 PP and lower hepatic antioxidant levels by d 28 PP. Supplementation with EFA+CLA had only a minor effect on oxidative markers, which were more similar to those with the EFA treatment. Altogether, despite the time-dependent differences, the current findings show only minor effects of EFA and CLA supplementation in the prevention of early lactation-induced oxidative stress.

Review: Effect of essential fatty acids and conjugated linoleic acid on the adaptive physiology of dairy cows during the transition period.

Cows fed total mixed rations (silage-based) may not receive as much essential fatty acids (EFAs) and conjugated linoleic acids (CLAs) as cows fed pasture-based rations (fresh grass) containing rich sources of polyunsaturated fatty acids. CLA-induced milk fat depression allows dairy cows to conserve more metabolisable energy, thereby shortening the state of negative energy balance and reducing excessive fat mobilisation at early lactation. EFAs, particularly α-linolenic acid, exert anti-inflammatory and antioxidative properties, thereby modulating immune functions. Thus, combined EFA and CLA supplementation seems to be an effective nutritional strategy to relieve energy metabolism and to improve immune response, which are often compromised during the transition from late pregnancy to lactation in high-yielding dairy cows. There has been extensive research on this idea over the last two decades, and despite promising results, several interfering factors have led to varying findings, making it difficult to conclude whether and under what conditions EFA and CLA supplementations are beneficial for dairy cows during the transition period. This article reviews the latest studies on the effects of EFA and CLA supplementation, alone or in combination, on dairy cow metabolism and health during various stages around parturition. Our review article summarises and provides novel insights into the mechanisms by which EFA and/or CLA influence markers of metabolism, energy homeostasis and partitioning, immunity, and inflammation revealed by a deep molecular phenotyping.

Evaluation of supplemental fat sources and pre-farrow essential fatty acid intake on lactating sow performance and essential fatty acid composition of colostrum, milk, and adipose tissue.

A total of 91 sows (Line 241, DNA Genetics) were used to evaluate the effects of supplemental fat sources and essential fatty acid intake on sow farrowing performance, litter growth performance, and essential fatty acid composition of colostrum, milk, and adipose tissue. At approximatelyday 107 of gestation, sows were blocked by body weight and parity, then allotted to 1 of 5 experimental treatments as part of a 2 × 2 + 1 factorial arrangement. Experimental diets were corn-soybean meal-based with a control diet that contained no added fat or diets with 3% added fat as either beef tallow or soybean oil, with consumption of the added fat diets starting on day 107 or 112 of gestation and fed until weaning. Thus, sows were provided low essential fatty acids (EFA; as linoleic and α-linolenic acid) without supplemental fat or with beef tallow or high EFA with soybean oil. Sows were provided approximately 2.8 kg/d of their assigned lactation diet pre-farrow and then provided ad libitum access after parturition. Sows consuming diets with beef tallow had greater lactation ADFI (fat source, P = 0.030), but lower daily linoleic acid (LA) and α-linolenic acid (ALA) intake than sows that consumed diets with soybean oil (fat source, P < 0.001). Supplemental fat sources providing either low or high EFA did not influence litter growth performance (fat source, P > 0.05). Sows fed diets with beef tallow did not influence the LA composition of colostrum; however, lactation diets with high EFA provided by soybean oil on day 107 of gestation increased colostrum LA concentration compared to providing diets on day 112 of gestation (fat source × time, P = 0.084; time, P < 0.001). Additionally, regardless of pre-farrow timing, ALA concentration of colostrum increased when sows consumed diets with soybean oil compared to beef tallow (fat source, P < 0.001). Both LA and ALA concentrations of milk at weaning were greater for sows that consumed diets with soybean oil compared to beef tallow (fat source, P < 0.001). Furthermore, concentrations of LA and ALA within adipose tissue were greater at weaning when sows consumed diets with high EFA compared to low EFA (fat source, P < 0.05). These responses suggest that providing dietary fat sources with high concentrations of EFA can increase backfat, colostrum, and milk LA and ALA. However, in this experiment, changes in colostrum and milk composition did not influence litter growth performance.

The lactating sow secretes essential fatty acids (EFA) in colostrum and milk to support litter growth and if dietary linoleic (LA) and alpha-linolenic acid (ALA) intake during lactation are limited, subsequent reproductive function of sows may be impaired. However, the inclusion of dietary fat sources with varying EFA composition in lactation diets provided shortly prior to farrowing can increase the energy density of the diet and modify colostrum and milk fatty acid profiles that may influence litter growth performance and survivability. The first objective of this trial was to evaluate the impact of providing sows lactation diets with dietary fat sources that provide low or high EFA on colostrum, milk, and sow adipose tissue fatty acid composition. A second objective was to evaluate the timing of feeding low- or high-EFA diets within the last week of gestation on colostrum and milk EFA composition. Overall, providing dietary fat sources with high concentrations of EFA shortly prior to farrowing altered fatty acid profiles of colostrum, milk, and backfat resulting in increased LA and ALA when compared to providing sows diets with low EFA. However, changes in colostrum and milk composition did not alter litter growth performance.

Evaluation of essential fatty acids in lactating sow diets on sow reproductive performance, colostrum and milk composition, and piglet survivability.

Mixed parity sows (n = 3,451; PIC, Hendersonville, TN; parities 2 through 9) and their litters were used to evaluate the effects of essential fatty acid (EFA) intake on sow reproductive performance, piglet growth and survivability, and colostrum and milk composition. Our hypothesis, like observed in earlier research, was that increasing linoleic acid (LA) and α-linolenic acid (ALA) would improve sow and litter performance. At approximately day 112 of gestation, sows were randomly assigned within parity groups to 1 of 4 corn-soybean meal-wheat-based lactation diets that contained 0.5 (Control) or 3% choice white grease (CWG), 3% soybean oil (SO), or a combination of 3% soybean oil and 2% choice white grease (Combination). Thus, sows were provided diets with low LA and ALA in diets with CWG or high LA and ALA in diets that included soybean oil. Sows received their assigned EFA treatments until weaning and were then fed a common gestation and lactation diet in the subsequent reproductive cycle. Average daily feed intake during the lactation period increased (P < 0.05) for sows fed the Combination and CWG diets compared with sows fed the Control or SO diet. However, daily LA and ALA intakes of sows fed the Combination and SO diets were still greater (P < 0.05) than those of sows fed 0.5 or 3% CWG. Overall, sows consuming high EFA from the Combination or SO diets produced litters with heavier (P < 0.05) piglet weaning weights and greater (P < 0.05) litter ADG when compared with litters from sows fed diets with CWG that provided low EFA. Despite advantages in growth performance, there was no impact of sow EFA intake on piglet survivability (P > 0.10). Additionally, lactation diet EFA composition did not influence sow colostrum or milk dry matter, crude protein, or crude fat content (P > 0.10). However, LA and ALA content in colostrum and milk increased (P < 0.05) in response to elevated dietary EFA from SO. There was no evidence for differences (P > 0.10) in subsequent sow reproductive or litter performance due to previous lactation EFA intake. In conclusion, increased LA and ALA intake provided by soybean oil during lactation increased overall litter growth and pig weaning weights, reduced sow ADFI, but did not affect piglet survivability or subsequent performance of sows.

Supplemental fat sources are an effective and widely accepted strategy to increase energy density of sow lactation diets that can also provide essential fatty acids such as linoleic acid (LA) and α-linolenic acid (ALA). Currently, the effects of supplemental LA and ALA provided shortly before farrowing on colostrum and milk composition are not fully understood. Additionally, the influence of elevated LA and ALA provided in sow lactation diets on litter growth and survivability responses has not been extensively evaluated. Therefore, this trial was conducted to evaluate the effects of fat sources providing low and high LA and ALA intake on sow performance, litter growth and survivability, colostrum and milk composition, and subsequent reproductive performance. Overall, sows consuming diets with high LA and ALA provided by soybean oil produced litters with heavier piglet weaning weights and greater litter average daily gain when compared with sows consuming diets with low LA and ALA content. Increasing LA and ALA by added soybean oil also increased their content in colostrum and milk. However, there was no influence of sow LA and ALA intake on litter survivability or subsequent reproductive performance of sows.

Cognitive improvement effect of nervonic acid and essential fatty acids on rats ingesting Acer truncatum Bunge seed oil revealed by lipidomics approach.

Acer truncatum Bunge seed oil (ASO) is rich in ω-9 (53.93%) and ω-6 (30.7%) fatty acids (FAs) and characterized by 3-7% nervonic acid (NA, C24:1ω-9). Evidence suggests that ω-9 FAs such as NA participate in processes of cognitive improvement; however, their mechanism remains ambiguous. In this study, we investigated the effect of ASO on rat memory and the change in lipid profiling and underlying metabolism. After ASO was administrated to rats for one, three and seven days, their capacity for learning and memory significantly increased via the MWM test. Lipid profiling showed alterations in a wide range of metabolic features after ASO was administrated to the rats, in which sphingolipids (SP) in the serum and glycerophospholipids (GP) in the brain were regulated significantly. The changes in the fatty acids in the serum and brain showed the synergetic effects of NA, EA, OA and DHA, where NA, EA and OA exhibited similar change trends. The enrichment analysis based on KEGG indicated that ASO supplementation evoked the pathways of neurotrophin signaling, glycerophospholipid metabolism and sphingolipid metabolism, which are related to memory and cognition improvement. Among the metabolites with different molecular forms, the biomarkers with C24:1ω-9 chains exhibited a positive correlation with others both in the serum SP and brain GP. These results suggest the synergistic effects of ω-9 FAs and that their conversion into each other may result in enhanced cognition in rats ingesting Acer truncatum Bunge seed oil.

Effect of essential fatty acid blend on circadian variations of ambulatory blood pressure in patients with essential hypertension and coronary artery disease risk markers.

Flaxseed oil is an excellent source of alpha-linolenic acid ALA known for its antihypertensive action. Flaxseed oil is unstable and its dose is not achievable in our conventional diet hence blending of natural flaxseed oil with palm oil, containing high flavonoids may be a better strategy, to stabilize the blend and provide proper balance of essential fatty acids and potential antioxidant effects. Aim of this study was to access the effect of blended flaxseed oil on 24 h 7-day circadian variations of blood pressure in subjects with essential hypertension. Assessment of CHAT (circadian hyper amplitude tension) using ABPM is the best marker for cardiovascular function. We registered 50 subjects with CAD (Group 1) and 50 subjects with Essential hypertension HT (Group 2) and 52 control subjects with CAD/Hypertension. Group 1 and 2 participant was supplemented with blended flaxseed oil (BFO) (30 ml/day) for the period of 24 weeks, while control group administered available oils sunflower in identical containers, for a follow-up period of 24 weeks. Twenty four hour seven days continuous ambulatory blood pressure monitoring was done initially and after six months of BFO supplementation. There were significant changes noted in lipid profile along with Ambulatory blood pressure parameters like MESOR, ACROPHASE, Hyperbaric Indexes, and CHAT. Circadian hyper amplitude tension (CHAT) incidence decreased after BFO supplementation. Study results suggest that blended flaxseed oil administration can be a potent natural vegetarian antihypertensive supplement which helps in synchronization of cardiac rhythms, and can be used as a preventive treatment of hypertension and as effective vegetarian source of maintaining Omega 3 and omega 6 ratios of essential fatty acids in the body.

Liver proteome profiling in dairy cows during the transition from gestation to lactation: Effects of supplementation with essential fatty acids and conjugated linoleic acids as explored by PLS-DA.

This study aimed at investigating the synergistic effects of essential fatty acids (EFA) and conjugated linoleic acids (CLA) on the liver proteome profile of dairy cows during the transition to lactation. 16 Holstein cows were infused from 9 wk. antepartum to 9 wk. postpartum into the abomasum with either coconut oil (CTRL) or a mixture of EFA (linseed + safflower oil) and CLA (EFA + CLA). Label-free quantitative proteomics was performed in liver tissue biopsied at days -21, +1, +28, and + 63 relative to calving. Differentially abundant proteins (DAP) between treatment groups were identified at the intersection between a multivariate and a univariate analysis. In total, 1680 proteins were identified at each time point, of which between groups DAP were assigned to the metabolism of xenobiotics by cytochrome P450, drug metabolism - cytochrome P450, steroid hormone biosynthesis, glycolysis/gluconeogenesis, and glutathione metabolism. Cytochrome P450, as a central hub, enriched with specific CYP enzymes comprising: CYP51A1 (d - 21), CYP1A1 & CYP4F2 (d + 28), and CYP4V2 (d + 63). Collectively, supplementation of EFA + CLA in transition cows impacted hepatic lipid metabolism and enriched several common biological pathways at all time points that were mainly related to ω-oxidation of fatty acids through the Cytochrome p450 pathway. SIGNIFICANCE: In three aspects this manuscript is notable. First, this is among the first longitudinal proteomics studies in nutrition of dairy cows. The selected time points are critical periods around parturition with profound endocrine and metabolic adaptations. Second, our findings provided novel information on key drivers of biologically relevant pathways suggested according to previously reported performance, zootechnical, and metabolism data (already published elsewhere). Third, our results revealed the role of cytochrome P450 that is hardly investigated, and of ω-oxidation pathways in the metabolism of fatty acids with the involvement of specific enzymes.

Effects of a combined essential fatty acid and conjugated linoleic acid abomasal infusion on metabolic and endocrine traits, including the somatotropic axis, in dairy cows.

The objective of this study was to test the effects of essential fatty acids (EFA), particularly α-linolenic acid (ALA), and conjugated linoleic acid (CLA) supplementation on metabolic and endocrine traits related to energy metabolism, including the somatotropic axis, in mid-lactation dairy cows. Four cows (126 ± 4 d in milk) were used in a dose-escalation study design and were abomasally infused with coconut oil (CTRL; 38.3 g/d; providing saturated fatty acids), linseed and safflower oils (EFA; 39.1 and 1.6 g/d; n-6:n-3 FA ratio = 1:3), Lutalin (CLA; cis-9,trans-11 and trans-10,cis-12 CLA, 4.6 g/d of each), or EFA and CLA (EFA+CLA) for 6 wk. The initial dosage was doubled twice after 2 wk, resulting in 3 dosages (dosages 1, 2, and 3). Each cow received each fat treatment at different times. Cows were fed with a corn silage-based total mixed ration providing a low-fat content and a high n-6:n-3 fatty acid ratio. Plasma concentrations of metabolites and hormones (insulin-like growth factor-binding proteins only on wk 0 and 6) were analyzed at wk 0, 2, 4, and 6 of each treatment period. Liver biopsies were taken before starting the trial and at wk 6 of each treatment period to measure hepatic mRNA abundance of genes linked to glucose, cholesterol and lipid metabolism, and the somatotropic axis. The changes in the milk and blood fatty acid patterns and lactation performance of these cows have already been published in a companion paper. The plasma concentration of total cholesterol increased with dosage in all groups, except CLA, reaching the highest levels in EFA+CLA and CTRL compared with CLA. The high-density lipoprotein cholesterol plasma concentration increased in CTRL and was higher than that in EFA and CLA, whereas the concentration of low-density lipoprotein cholesterol increased in a dose-dependent manner in EFA and EFA+CLA, and was higher than that in CLA. Hepatic mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA synthase 1 was upregulated in all groups but was highest in EFA+CLA. Expression of sterol regulatory element-binding factor 1 tended to be lowest due to EFA treatment, whereas expression of long chain acyl-CoA-synthetase was lower in EFA than in CTRL. Hepatic mRNA expression of GHR1A tended to be higher in EFA+CLA than in CTRL. The plasma concentration of insulin-like growth factor I increased in CLA, and the plasma IGFBP-2 concentration was lower in EFA+CLA than in CTRL at wk 6. The plasma concentration of adiponectin decreased in EFA+CLA up to dosage 2. Plasma concentrations of albumin and urea were lower in CLA than in CTRL throughout the experimental period. Supplementation with EFA and CLA affected cholesterol and lipid metabolism and their regulation differently, indicating distinct stimulation after the combined EFA and CLA treatment. The decreased IGFBP-2 plasma concentration and upregulated hepatic mRNA abundance of GHR1A in EFA+CLA-supplemented cows indicated the beneficial effect of the combined EFA and CLA treatment on the somatotropic axis in mid-lactation dairy cows. Moreover, supplementation with CLA might affect protein metabolism in dairy cows.

Effects of abomasal infusion of essential fatty acids together with conjugated linoleic acid in late and early lactation on performance, milk and body composition, and plasma metabolites in dairy cows.

Rations including high amounts of corn silage are currently very common in dairy production. Diets with corn silage as forage source result in a low supply of essential fatty acids, such as α-linolenic acid, and may lead to low conjugated linoleic acid (CLA) production. The present study investigated the effects of abomasal infusion of essential fatty acids, especially α-linolenic acid, and CLA in dairy cows fed a corn silage-based diet on performance, milk composition, including fatty acid (FA) pattern, and lipid metabolism from late to early lactation. Rumen-cannulated Holstein cows (n = 40) were studied from wk 9 antepartum to wk 9 postpartum and dried off 6 wk before calving. The cows were assigned to 1 of 4 treatment groups. Cows were abomasally supplemented with coconut oil (CTRL, 76 g/d), linseed and safflower oil (EFA, 78 and 4 g/d; linseed/safflower oil ratio = 19.5:1; n-6/n-3 FA ratio = 1:3), Lutalin (CLA, 38 g/d; BASF SE, Ludwigshafen, Germany; isomers cis-9,trans-11 and trans-10,cis-12 each 10 g/d) or EFA+CLA. Milk composition was analyzed weekly, and blood samples were taken several times before and after parturition to determine plasma concentrations of metabolites related to lipid metabolism. Liver samples were obtained by biopsy on d 63 and 21 antepartum and on d 1, 28, and 63 postpartum to measure triglyceride concentration. Body composition was determined after slaughter. Supplementation of CLA reduced milk fat concentration, increased body fat mass, and improved energy balance (EB) in late and early lactation, but EB was lowest during late lactation in the EFA group. Cows with CLA treatment alone showed an elevated milk citrate concentration in early lactation, whereas EFA+CLA did not reveal higher milk citrate but did have increased acetone. Milk protein was increased in late lactation but was decreased in wk 1 postpartum in CLA and EFA+CLA. Milk urea was reduced by CLA treatment during the whole period. After calving, the increase of nonesterified fatty acids in plasma was less in CLA groups; liver triglycerides were raised lowest at d 28 in CLA groups. Our data confirm an improved metabolic status with CLA but not with exclusive EFA supplementation during early lactation. Increased milk citrate concentration in CLA cows points to reduced de novo FA synthesis in the mammary gland, but milk citrate was less affected in EFA+CLA cows, indicating that EFA supplementation may influence changes in mammary gland FA metabolism achieved by CLA.

The Sources of Essential Fatty Acids for Allergic and Cancer Patients; a Connection with Insight into Mammalian Target of Rapamycin: A Narrative Review

Background: Disturbance in essential fatty acids (EFA) metabolism plays a key role in autoimmune diseases, but EFA supplementation with sources of borage, evening primrose, hemp seed and fish oils was not effective in atopic and cancer diseases, as that seen in the case of multiple sclerosis. It seems that two complexes of the mammalian target of rapamycin (mTOR) signaling, mTORC1 and mTORC2, are congruent with the two bases of the Traditional Iranian Medicine (TIM) therapy, Cold and Hot nature, which are essential for the efficacy of functional oils for controlling immune responses in autoimmune diseases. Methods: We searched PubMed database, Web of Science (WOS), Google Scholar, Scopus and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. Results: The oils controlled by Cold or Hot nature may be helpful in maintaining homeostasis and preventing autoimmune diseases. In summary, studies of randomized controlled trials for allergy and cancer patients found no improvement in the signs or response to tests, despite a remarkable change in EFA fractions in the blood by supplementation with sources of borage, evening primrose, hemp seed and fish oils. In contrast, portulaca oleracea oil exhibited protective effects by anti-inflammatory properties via the PI3K/Akt/mTORC2 pathway with a deviation immune response to Th1 to treat atopic diseases and cancer. Conclusions: According to the concept of Traditional Iranian Medicine therapy, in contrast to Cold-nature oils, EFA supplementation with the sources of Hot-nature oilsis not suitable for the treatment of atopic and cancerous diseases.

A Combination of Essential Fatty Acids, Panax Ginseng Extract, and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults.

OBJECTIVES: To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults. DESIGN: Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period. SETTING: The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center. PARTICIPANTS: Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years). INTERVENTION: Daily consumption of an investigational product (trade name "Cerbella TM") consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients. MEASUREMENTS: Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm. RESULTS: Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p<.05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity. CONCLUSION: One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.

Controversies in the Use of Lipid Injectable Emulsion in Hospitalized Patients.

Soybean oil-based lipid injectable emulsion (SO-based ILE) is an 18-carbon, ω-6 macronutrient providing a concentrated source of calories, which can be administered in or with parenteral nutrition to patients unable to tolerate or consume adequate enteral nutrition. Beyond the provision of energy, SO-based ILE provides linoleic and linolenic acid, 2 essential fatty acids necessary for the prevention of essential fatty acid deficiency. However, SO-based ILE with its high levels of ω-6 fatty acids, long-chain triglycerides, phospholipid emulsifiers, and glycerin has been associated with worsening clinical outcomes, including increase of infections, lengthier intensive care and hospital stay, and prolonged mechanical ventilation. Recognizing this, studies have investigated omitting SO-based ILE in the critically ill patient for the first 7 days to observe if clinical outcomes are improved. Unfortunately, there is extremely limited research, and what is available is controversial. National guidelines have analyzed the studies, and they too are challenged to define a clear, high quality of evidence recommendation. It is important for the healthcare clinician to understand the research around this controversy to make best decisions for their patients.

The molecular basis of essential fatty acid limitation in Daphnia magna: A transcriptomic approach.

It is widely accepted that in many food webs, the trophic transfer efficiency among primary producers and herbivores is determined by the nutritional value of primary producers. In pelagic freshwater and marine ecosystems, secondary production by herbivorous crustacean zooplankton is often limited by the seston's content of essential ω3 polyunsaturated fatty acids (ω3 PUFAs). However, little is known about the genetic network behind the positive relationship between phytoplankton ω3 PUFA content and zooplankton growth and reproduction. In our experimental study, we analysed gene expression changes of the freshwater cladoceran Daphnia magna under different food regimes differing in their ω3 PUFA composition. To disentangle ω3 PUFA effects from other factors, we fed D. magna with different pure phytoplankton cultures (i.e., algal and cyanobacterial diets) with or without supplementing the essential ω3 PUFA eicosapentaenoic acid (EPA). As hypothesized, we observed enhanced growth on diets supplemented with EPA. We applied an Illumina RNA-seq approach to D. magna from different diet treatments to find and monitor genes that are regulated dependent on EPA availability. Of 26,646 potential protein products (mapped to the D. magna genome), we identified transcriptomic signatures driven by the different food sources. Further analyses revealed specific candidate genes involved in EPA metabolism, irrespective of the basal food source. This allows a first functional annotation of previously uncharacterized genes involved in the EPA-specific response of D. magna and may finally provide a link to molecular processes connected to ω3 PUFA metabolism and conversion and thus trophic transfer efficiency in pelagic food webs.

Prenatal Lipid-Based Nutrient Supplements Do Not Affect Pregnancy or Childbirth Complications or Cesarean Delivery in Bangladesh: A Cluster-Randomized Controlled Effectiveness Trial.

Background: Pregnancy and childbirth complications and cesarean delivery are common in Bangladesh.Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on pregnancy and childbirth complications and cesarean delivery.Methods: We conducted the Rang-Din Nutrition Study, a cluster-randomized controlled effectiveness trial within a community health program in rural Bangladesh. We enrolled 4011 pregnant women in early pregnancy. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 µg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Pregnancy and childbirth complications and the cesarean delivery rate were secondary outcomes of the study.Results: Women in the LNS-PL group did not differ significantly from the IFA group with respect to mean systolic blood pressure at 36 wk gestation (113 and 112 mm Hg; P = 0.17), diastolic blood pressure at 36 wk gestation (68.9 and 68.7 mmHg; P = 0.88), or mean total number of pregnancy and childbirth complications (0.32 and 0.31; P = 0.86). They also did not differ significantly with respect to the prevalence of high blood pressure at 36 wk (1.74% and 2.03%; P = 0.62), antepartum hemorrhage (0.83% and 1.39%; P = 0.21), prolonged labor (8.34% and 8.79%; P = 0.68), early rupture of membranes (9.30% and 8.45%; P = 0.43), convulsions (1.57% and 1.08%; P = 0.24), high blood pressure in labor (1.54% and 1.19%; P = 0.46), obstructed labor (2.83% and 2.91%; P = 0.90), any complications during pregnancy or childbirth (35.9% and 37.1%; P = 0.64), episiotomy (6.31% and 6.44%; P = 0.90), or cesarean delivery (15.6% and 14.2%; P = 0.48).Conclusion: Compared with IFA, antenatal LNS-PL did not increase or decrease pregnancy and childbirth complications or cesarean delivery among women in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038.

Polyunsaturated Fatty Acids Differentially Modulate Cell Proliferation and Endocannabinoid System in Two Human Cancer Lines.

BACKGROUND AND AIMS: Evidence suggests that quantity and quality of dietary polyunsaturated fatty acids (PUFAs) play a role in the development of cancer. However, the mechanisms involved in this interaction(s) are not clear. Endocannabinoids are lipid metabolites known to have growth modulatory actions. We studied the effect of supplementation with PUFAs ω-6 and ω-3 (essential fatty acids, EFAs), saturated and monounsaturated fatty acids (non-EFAs) on the growth of tumor cells and modifications in their endocannabinoid content. METHODS: Cell cultures of human glioblastoma (T98G) and breast cancer (MCF7) were supplemented with 50 or 100 mmol EFAs and non-EFAs for 72 h. Cell proliferation was then determined by MTT, anandamide (AEA) levels by HPLC, total fatty acids profiles by GLC, CB1 receptor expression by WB and FAAH activity by spectrophotometric method. RESULTS: Fatty acids profile reflected the incorporation of the lipids supplemented in each assay. Arachidonic acid (EFA ω-6) supplementation increased AEA levels and inhibited the growth of T98G, whereas palmitic acid (non-EFA) enhanced their proliferation. In breast cancer (MCF7) cells, eicosapentaenoic acid (EFA ω-3) reduced and oleic acid (non-EFA) enhanced their proliferation. CB1 expression was higher in T98G and no differences were observed in FAAH activity. CONCLUSIONS: The growth of tumor cells can be differentially modulated by fatty acids and, at least in part, can be attributed to their ability to act on the components of the endocannabinoid system.

Effect of 12-month intervention with lipid-based nutrient supplement on the physical activity of Malawian toddlers: a randomised, controlled trial.

Physical activity is beneficial for children's well-being. The effect of dietary supplementation on children's physical activity in food-insecure areas remains little studied. We examined the effects of a lipid-based nutrient supplement (LNS) on children's objectively measured physical activity in a randomised, controlled, outcome-assessor-blinded trial. Mothers of the children received one capsule daily of Fe-folic acid (IFA), one capsule containing eighteen micronutrients (MMN) or one 20 g sachet of LNS (containing twenty-two MMN, protein, carbohydrates, essential fatty acids and 494 kJ (118 kcal)) during pregnancy and for 6 months thereafter. Children in the IFA and MMN groups received no supplementation, and these groups were collapsed into a single control group; children in the LNS group received 20 g LNS from 6 to 18 months. We measured physical activity with accelerometers over 1 week at 18 months. The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months, 570 (78 %) provided sufficient data for analysis. The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 (sd 59) and 301 (sd 56), respectively (P for difference=0·65). LNS, given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age, did not increase physical activity among 18-month-old children.

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Comparação dos efeitos do ácido hialurônico 0, 2% e ácidos graxos essenciais em paciente com queimadura por fertilizante: relato de caso / Comparison of the effects of hyaluronic acid 0. 2% and essential fatty acids in burn victim due to fertilizer exposure: case report / Comparación de los efectos del ácido hialurónico 0, 2% y los ácidos grasos esenciales en víctima de quemaduras debido a la exposición a fertilizante: relato de caso

Objetivo: Relatar a experiência no tratamento de queimadura decorrente de exposição a fertilizante, comparando o uso de creme de ácido hialurônico (AH) e ácidos graxos essenciais (AGE), em paciente atendido pelo programa Estratégia Saúde da Família (ESF) de Jaguariúna, SP. Relato de caso: P.C.M., sexo masculino, 46 anos, com queimaduras de 2o grau superficial e pequenas áreas de 2o grau profundo nas duas mãos, decorrentes do uso de fertilizante, sem sinais de infecção ou demais complicações. Foi atendido em Unidade de ESF, onde foi iniciado protocolo de limpeza diária das lesões com soro fisiológico 0,9%. Na mão direita, foi aplicada fina camada de AH 0,2% e, na mão esquerda, AGE, na mesma frequência de uso do AH. Os curativos foram feitos pela enfermeira e técnica da ESF. A evolução da reparação da lesão foi acompanhada e avaliada diariamente por esses profissionais. Resultados: Após 60 dias de uso tópico de creme contendo AH 0,2%, ocorreu a completa cicatrização da mão direita. Na mesma data de avaliação, a mão esquerda ainda apresentava fissuras e descamação, não demonstrando total cicatrização. Com a piora do quadro da mão esquerda, optou-se por suspender o uso do AGE e iniciar o uso de AH uma vez ao dia. Após 39 dias, foi verificado que a lesão estava completamente cicatrizada. Conclusão: Os resultados demonstraram que o uso de AH proporcionou cicatrização de forma mais rápida e efetiva para queimadura decorrente da exposição a fertilizante, em comparação ao AGE.

Objective: To report the experience in treating a burn victim due to fertilizer exposure comparing hyaluronic acid (HA) cream and essential fatty acids (EFA), who was treated by Health Family Strategy (HFS) of Jaguariuna, SP. Case report: P.C.M., male, 46 years old, with superficial second-degree burn injuries and small areas with deep second degree burn on both hands, caused by fertilizer exposure. There were no signs of infection or other complications. He was treated at HFS Unit where a protocol to clean the wound with saline solution 0.9% was initialized. On his right hand was applied HA 0.2% and on his left hand was applied EFA following the same routine in both hands. A nurse and a technical nurse of the HFS Unit did all the dressings and evaluated the wounds daily. Results: The complete reparation of the injury on the right hand was achieved after 60 days applying HA 0.2%. In the same period, the left hand was still not fully recovered and presented fissure and peeling, with this result the nurses decided to suspend the EFA and start using HA on the left hand once a day. After 39 days, the left hand was entirely recovered. Conclusion: These results demonstrate that the use of HA provided healing more quickly and effectively to burn due to exposure to fertilizer, as compared to the EFA.

Objetivo: Presentar la experiencia en el tratamiento de quemaduras debido a la exposición a fertilizante, comparando el uso de la crema de ácido hialurónico(AH) y ácidos grasos esenciales(AGE),en pacientes atendidos por el Estratégia Saúde da Família(ESF) en la ciudad de Jaguariúna, São Paulo. Relato de caso: P.C.M., varón, de 46 años, con quemaduras de segundo grado superficiales y pequeñas áreas de segundo grado profundo en ambas manos, como resultado del uso de fertilizantes, sin signos de infección u otras complicaciones. El paciente fue tratado en la Unidad ESF, donde se inició el protocolo de limpieza diaria de las lesiones con solución salina al 0,9%. En su mano derecha se aplicó una capa fina de AH 0,2% y en la mano izquierda, AGE, en la misma frecuencia del uso de AH. Las curaciones fueron realizadas por la enfermera y la técnica de enfermería de ESF. La evolución del reparo de la lesión fue acompañada y evaluada diariamente por esos profesionales. Resultados: Después de 60 días de utilización de AH 0,2% em crema, se observó completa cicatrización de la mano derecha. En la misma data, la mano izquierda aún presentaba grietas y descamación, no siendo observado cicatrización completa. Con la imagen de la izquierda empeoramiento, se decidió suspender el uso del AGE y comenzar a usar AH una vez al día. Después de 39 días, se encontró que la lesión se curó completamente. Conclusión: Estos resultados demuestran que el uso de HA proporciona una curación más rápida y efectiva para quemaduras debido a la exposición a fertilizantes en comparación con la AGE.