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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.

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 MIC 50/90 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 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Wang, Li, Wang, Su, Gu and Wang.)

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 β-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., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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 Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

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., (Creative Commons Attribution License)

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., (© 2018 American Society for Parenteral and Enteral Nutrition.)

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., (© 2018 John Wiley & Sons Ltd.)

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., Competing Interests: Dr. Carmichael received contract support from Neurodyn, Inc. for the conduct of the reported clinical trial on Cerbella (TM), for travel, for data analysis, and for the writing of this manuscript. Cerbella (TM) is a Neurodyn, Inc. product. Dr. Carmichael also received funding from the Pennington Biomedical Research Foundation. Dr. Gold has nothing to disclose. Dr. McLellan reports personal fees from Neurodyn and grants from ACOA during the conduct of the study; personal fees from Neurodyn outside the submitted work. In addition, Dr. McLellan has a patent 62460021 pending related to this manuscript.Dr. Keller received contract support from Neurodyn, Inc. for the conduct of the reported clinical trial on Cerbella (TM). Cerbella (TM) is a Neurodyn, Inc. product. Sreekrishna Pillai has nothing to disclose. Dr. Shankapal has nothing to disclose. Dr. Kay reports personal fees from Neurodyn and grants from ACOA during the conduct of the study; personal fees from Neurodyn outside the submitted work. In addition, Dr. Kay has a patent 62460021 pending related to this manuscript.

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.

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., Competing Interests: Author disclosures: MKM, SLM, RRP, SH, MS, MH, JMP, SAV, and KGD, no conflicts of interest., (© 2017 American Society for Nutrition.)

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.

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., (Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.)

We previously reported the importance of long-chain polyunsaturated fatty acid (LC-PUFA (>C20)) intake, including arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), for growth. This follow-up study focuses on ARA using a novel artificial rearing model during the lactation period in delta-6-desaturase knockout (D6D-KO) mice. Newborn D6D-KO male mouse pups were separated from dams within 48 hours and fed artificial milks containing 18-C essential fatty acids (EFAs) (16-17% LA, 3.8-4.1% ALA) with or without 1.2% ARA. After weaning, mice were maintained on similar diets: 15% LA, 2.3-2.4% ALA with or without 1.9% ARA. As a reference group, new born wild type (WT) male mouse pups were maintained by artificial milk and diet containing LA and ALA without ARA. Aspects of brain function were measured behaviorally (motor activity and rota-rod test) when mice were age 9 weeks. Body weight in the KO-Cont group was significantly lower (approximately 30%) than in the WT-Cont group, but this decrease was ameliorated by providing ARA in the KO-ARA group. The motor activity and coordination in the KO-Cont group decreased markedly compared to the WT-Cont group. The KO-ARA group had a tendency toward deteriorated motor coordination, although the motor activity was significantly enhanced compared to the KO-Cont group. In KO-ARA group brains, the level of ARA was increased and DHA decreased compared to WT-Cont. These results suggest that intake of LA and ALA only is insufficient to support healthy growth, and that ARA is also required, at least during the lactation period. These findings also suggested that continued intake of relatively high levels of ARA and without supplemental DHA during development led to an increased motor activity above that of WT animals. These studies indicate that both ARA dose and proper combination with DHA must be delineated to define optimal growth and behavioral function., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Recently, the European Food Safety Authority asserted that arachidonic acid (ARA) is an optional nutrient for the term infant even when docosahexaenoic acid (DHA) is present. The brief rationale is based on an explicit, widespread misapplication of the concept of "essential fatty acids" to linoleic acid that implies it is uniquely required as a nutrient per se. Linoleic acid prevents acute clinical symptoms caused by polyunsaturated fatty acid-deficient diets and is the major precursor for ARA in most human diets. Experimental diets with ARA as the sole n-6 similarly prevent symptoms but at a lower energy percentage than linoleic acid and show ARA is a precursor for linoleic acid. The absence of consistent evidence of ARA benefit from randomized controlled trials is apparently an issue as well. This review highlights basic and clinical research relevant to ARA requirements as an adjunct to DHA in infancy. ARA is a major structural central nervous system component, where it rapidly accumulates perinatally and is required for signaling. Tracer studies show that ARA-fed infants derive about half of their total body ARA from dietary preformed ARA. Clinically, of the 3 cohorts of term infants studied with designs isolating the effects of ARA (DHA-only vs DHA+ARA), none considered ARA-specific outcomes such as vascular or immune function; the study with the highest ARA level showed significant neurocognitive benefit. All breastfed term infants of adequately nourished mothers consume both DHA and ARA. The burden of proof to substantially deviate from the composition of breastmilk is greater than that available from inherently empirical human randomized controlled trial evidence. Infant formulas with DHA but without ARA risk harm from suppression of ARA-mediated metabolism manifest among the many unstudied functions of ARA., (© The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study was conducted to investigate the effects of supplemental essential fatty acids (EFA) on sow reproductive efficiency and to estimate the concentrations of EFA required by the lactating sow for maximum subsequent reproduction. Data were collected on 480 sows (PIC Camborough) balanced by parity, with 241 and 239 sows representing Parity 1, and 3-5 (P3+), respectively. Sows were assigned randomly, within parity, to a 3 × 3 factorial arrangement plus a control diet without added lipids. Factors included linoleic (2.1%, 2.7%, and 3.3%) and α-linolenic acid (0.15%, 0.30%, and 0.45%), obtained by adding 4% of different mixtures of canola, corn and flaxseed oils to diets. Diets were corn-soybean meal based with 12% wheat middlings. The benefits of supplemental EFA were more evident for the subsequent reproduction of mature P3+ sows. For these sows, supplemental α-linolenic acid improved the proportion of sows that farrowed relative to sows weaned (linear P=0.080; 82.8, 80.5, and 92.8% for sows fed 0.15%, 0.30%, and 0.45% α-linolenic acid, respectively). In addition, supplemental linoleic acid, fed to Parity 1 and P3+ sows, tended to increase subsequent litter size (linear P=0.074; 13.2, 13.8 and 14.0 total pigs born for 2.1%, 2.7% and 3.3% linoleic acid, respectively). These results demonstrate that a minimum dietary intake of both α-linolenic and linoleic acid is required for the modern lactating sow to achieve a maximum reproductive outcome through multiple mechanisms that include rapid return to estrus, increased maintenance of pregnancy and improved subsequent litter size., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Low intakes of good-quality complementary foods (CFs) contribute to undernutrition and consequently negatively affect health, growth, and development. Lipid-based nutrient supplements (LNSs) are designed to ensure dietary adequacy in micronutrients and essential fatty acids and to provide some energy and high-quality protein. In populations in which acute energy deficiency is rare, the dose-dependent effect of LNSs on CF intakes is unknown., Objective: The objective of this study was to evaluate the difference in energy and macronutrient intakes from CF between a control (no supplement) group and 3 groups that received 10, 20, or 40 g LNS/d., Methods: We collected repeated interactive 24-h dietary recalls from caregivers of rural Malawian 9- to 10-mo-old infants (n = 748) to estimate dietary intakes (LNS and all non-breast-milk foods) of energy and macronutrients and their dietary patterns. All infants were participating in a 12-mo randomized controlled trial to investigate the efficacy of various doses of LNS for preventing undernutrition., Results: Dietary energy intakes were significantly higher among infants in the LNS intervention groups than in the control group (396, 406, and 388 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d; each pairwise P < 0.05), but no significant differences were found in energy intakes between groups who were administered the different LNS doses (10 g LNS/d compared with 20 g LNS/d: P = 0.72; 10 g LNS/d compared with 40 g LNS/d: P ≥ 0.67; 20 g LNS/d compared with 40 g LNS/d: P = 0.94). Intakes of protein and fat were significantly higher in the LNS intervention groups than in the control group. No significant intergroup differences were found in median intakes of energy from non-LNS CFs (357, 347, and 296 kcal/d in the 10-, 20-, and 40-g LNS/d groups, respectively, compared with 345 kcal/d in the control group; P = 0.11)., Conclusion: LNSs in doses of 10-40 g/d increase intakes of energy and macronutrients among 9- to 10-mo-old Malawian infants, without displacing locally available CFs. This trial was registered at clinicaltrials.gov as NCT00945698., (© 2016 American Society for Nutrition.)

The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum-epidermis and the epidermis-dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Resolution of acute inflammation is an active process locally controlled by a novel genus of specialized pro-resolving mediators (SPM) that orchestrate key resolution responses. Hence, it is of general interest to identify individual bioactive mediators and profile their biosynthetic pathways with related isomers as well as their relation(s) to classic eicosanoids in mammalian tissues. Lipid mediator (LM)-SPM levels and signature profiles of their biosynthetic pathways were investigated using liquid chromatography-tandem mass spectrometry (LC-MS-MS)-based LM metabololipidomics. LM and SPM were identified using ≥6 diagnostic ions and chromatographic behavior matching with both authentic and synthetic materials. This approach was validated using the composite reference plasma (SRM1950) of 100 healthy individuals. Using targeted LM metabololipidomics, we profiled LM and SPM pathways in human peripheral blood (plasma and serum) and lymphoid organs. In these, we identified endogenous SPM metabolomes, namely, the potent lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR). These included RvD1, RvD2, RvD3, MaR1, and NPD1/PD1, which were identified in amounts within their bioactive ranges. In plasma and serum, principal component analysis (PCA) identified signature profiles of eicosanoids and SPM clusters. Plasma-SPM increased with omega-3 and acetylsalicylic acid intake that correlated with increased phagocytosis of Escherichia coli in whole blood. These findings demonstrate an approach for identification of SPM pathways (e.g., resolvins, protectins, and maresins) in human blood and lymphoid tissues that were in amounts commensurate with their pro-resolving, organ protective, and tissue regeneration functions. LM metabololipidomics coupled with calibration tissues and physiological changes documented herein provide a tool for functional phenotypic profiling., (Copyright © 2014 the American Physiological Society.)

Omega fatty acids and zinc contribute to physiological pathways that could affect the farrowing process, stillbirth, preweaning mortality, and postweaning return to estrus. To determine effects of omega fatty acids and zinc on these reproductive traits, gilts were mated and fed either a control diet, a diet supplemented with 1.09% Gromega, a diet supplemented with 0.07% zinc sulfate, or a diet supplemented with both Gromega and zinc sulfate from d 80 of gestation until farrowing. Farrowings were video recorded to obtain birth intervals for each piglet, and the number of live and stillborn piglets was recorded. On d 1 after farrowing, piglets were weighed, and the smallest piglet in each litter was sacrificed. A blood sample was collected to measure the immunoglobulin immunocrit ratio, and brain, cerebellum, brain stem, full and empty stomach (to calculate stomach content weight), and heart weights were recorded. Because myelination of specific brain regions may affect preweaning mortality, brain stem, cerebellum, and spinal cord tissues were measured for content of myelin basic proteins and myelin lipids. For remaining piglets, survival to weaning and weaning weights were recorded. Results indicated a weak positive correlation (r = 0.23, P < 0.05) between immunocrit values and brain stem high molecular weight myelin basic protein. There was also a Gromega × zinc supplementation interaction (P < 0.05) on brain stem high molecular weight myelin basic protein in which the combined treatment was greater than the control or each supplement alone. Zinc treatment decreased stillbirth rate during prolonged farrowing and subsequent preweaning survival of low birth weight piglets. Gromega increased overall stillbirth rate and increased the stillbirth rate during prolonged farrowing. There were no relationships between myelin measurements and preweaning survival. In conclusion, combined Gromega and zinc supplementation appeared to improve myelination, but zinc alone improved stillbirth and preweaning survival.

Stem cell therapy holds great promise for regenerative medicine and the treatment of numerous diseases. A key issue of stem cell therapy is the control of stem cell fate, but safe and practical methods are limited. Essential fatty acids, namely ω-6 (n-6) and ω-3 (n-3) polyunsaturated fatty acids (PUFA), and their metabolites are critical components of cell structure and function, and could therefore influence stem cell fate. The available evidence demonstrates that n-6 and n-3 PUFA and their metabolites can act through multiple mechanisms to promote the proliferation and differentiation of various stem cell types. Therefore, elucidating the role of PUFA and their metabolites in stem cell fate regulation is both a challenge and an opportunity for stem cell biology as well as stem cell therapy. PUFA-based interventions to create a favorable environment for stem cell proliferation or differentiation may thus be a promising and practical approach to controlling stem cell fate for clinical applications., (© 2013 AlphaMed Press.)

Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM) patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN) seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics--non-steroidal anti-inflammatory drugs (NSAIDS) and opioids--understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management.

Cells grown in culture are frequently employed to model lipid metabolism in vivo. There are reasons of convenience for this but examination of the lipidome of cultured cells and their metabolic responses to lipid supplementation give cause to indicate disparity with their counterparts in living animals. The reason is mainly that homeostatic regulation is exercised in animals supplied with an adequate diet in which the adipose tissue and liver represent plentiful sources of lipid integrated via inter-organ collaboration and able to buffer transient fluctuations in dietary lipid and essential fatty acids (EFAs). Moreover, conventional culture media are generally deficient in total lipids as well as essential EFAs. Cultured cells exposed to high glucose concentrations and lipid deficit typically manifest accelerated rates of lipogenesis evidenced by high rates of de novo FA biosynthesis. A more realistic model may be obtained by increasing supplements of lipid especially enriched in essential EFAs in the growth medium. Increasing concentrations of ω3 FAs, in particular, attenuate the rate of de novo lipogenesis. The improvement of cell culture models for pharmacological screening of drug-candidates targeting lipid or glucose metabolism is highlighted., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects more than five million Americans and is characterized by a progressive loss of memory, loss of cholinergic neurons in the basal forebrain, formation of amyloid plaques and neurofibrillary tangles, and an increase in oxidative stress. Recent studies indicate that dietary supplements of antioxidants and omega-3 and omega-6 fatty acids may reduce the cognitive deficits in AD patients. The current study tested a combinatorial treatment of antioxidants from tart cherry extract and essential fatty acids from Nordic fish and emu oils for reducing cognitive deficits in the mu-p75 saporin (SAP)-induced mouse model of AD. Mice were given daily gavage treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil) or vehicle (methylcellulose) for 2 weeks before intracerebroventricular injections of the cholinergic toxin, mu-p75 SAP, or phosphate-buffered saline. The TBR treatments continued for an additional 17 days, when the mice were tested on a battery of cognitive and motor tasks. Results indicate that TBR decreased the SAP-induced cognitive deficits assessed by the object-recognition, place-recognition, and Morris-water-maze tasks. Histological examination of the brain tissue indicated that TBR protected against SAP-induced inflammatory response and loss of cholinergic neurons in the area around the medial septum. These findings indicate that TBR has the potential to serve as an adjunctive treatment which may help reduce the severity of cognitive deficits in disorders involving cholinergic deficits, such as AD.

Human platelet-type 12-lipoxygenase (12-LOX) has recently been shown to play an important role in regulation of human platelet function by reacting with arachidonic acid (AA). However, a number of other fatty acids are present on the platelet surface that, when cleaved from the phospholipid, can be oxidized by 12-LOX. We sought to characterize the substrate specificity of 12-LOX against six essential fatty acids: AA, dihomo-γ-linolenic acid (DGLA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), eicosadienoic acid (EDA), and linoleic acid (LA). Three fatty acids were comparable substrates (AA, DGLA, and EPA), one was 5-fold slower (ALA), and two showed no reactivity with 12-LOX (EDA and LA). The bioactive lipid products resulting from 12-LOX oxidation of DGLA, 12-(S)-hydroperoxy-8Z,10E,14Z-eicosatrienoic acid [12(S)-HPETrE], and its reduced product, 12(S)-HETrE, resulted in significant attenuation of agonist-mediated platelet aggregation, granule secretion, αIIbβ3 activation, Rap1 activation, and clot retraction. Treatment with DGLA similarly inhibited PAR1-mediated platelet activation as well as platelet clot retraction. These observations are in surprising contrast to our recent work showing 12(S)-HETE is a prothrombotic bioactive lipid and support our hypothesis that the overall effect of 12-LOX oxidation of fatty acids in the platelet is dependent on the fatty acid substrates available at the platelet membrane.

The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acute insulin response during IVGTT (P = .0871). Soybean oil increased glucose at 30 (P = .0030) and 60 minutes (P = .0121) and AUC for glucose (P = .0122) during OGTT, tended to decrease acute insulin response during IVGTT (P = .0848), reduced testosterone (P = .0216), and tended to reduce sex hormone-binding globulin (P = .0858). Fasting glucose, insulin, adiponectin, leptin, or high-sensitivity C-reactive protein did not change with any intervention. Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably., (Published by Elsevier Inc.)

In order to compare the stimulation ability of insulin secretion, we determined changes in plasma glucose and insulin concentrations after intravenous administration of various amino acids and essential fatty acids in clinically healthy adult cats. Plasma glucose concentrations were within the normal ranges after injection of amino acids and fatty acids. Plasma insulin concentrations increased rapidly 2 to 4 min after injection of arginine, then decreased to the basal levels at 20 min in all five cats. Insulin peak responses were significantly greater in arginine injections than in normal saline (P<0.01). Areas under the curve (AUC) of plasma insulin concentrations from 0 to 10 min after injection of arginine were significantly larger than after injection of normal saline (P<0.01) and glucose (P<0.05). Increases in AUC of plasma insulin concentration from 0 to 60 min were observed after injection of arginine, leucine, alanine, and fat emulsion. Arginine had a strong insulinotropic effect, and leucine, alanine, and fatty acids had weak ones. Besides, valine, methionine, taurine and glutamine had no stimulant activity of insulin. Given the risk of glucose toxication and required time for testing, the intravenous arginine tolerance test may be useful for estimation of insulin responses in cats.

Psychiatric disorders are a significant source of disability worldwide. Increasing evidence indicates that disturbances of fatty acids and phospholipid metabolism can play a part in a wide range of psychiatric, neurological, and developmental disorders in adults. Essential fatty acids, ω-3 and ω-6 polyunsaturated fatty acids, play a central role in the normal development and functioning of the brain and central nervous system. The aim of this article is to discuss the overall insight into roles of essential fatty acids in the development of mental disorders (depression, schizophrenia, bipolar disorder) and, in light of the fact that disturbances of fatty acid metabolism can play a part in the above-mentioned disorders, to investigate the current knowledge of lipid abnormalities in posttraumatic stress disorder. The information in this review was obtained after extensive MEDLINE searching of each topic area through relevant published studies from the past 20 years. References from the obtained studies were also used. This review summarizes the knowledge in terms of essential fatty acids intake and metabolism, as well as evidence pointing to potential mechanisms of essential fatty acids in normal brain functioning and development of neuropsychiatric disorders. The literature shows that ω-3 fatty acids provide numerous health benefits and that changes in their concentration in organisms are connected to a variety of psychiatric symptoms and disorders, including stress, anxiety, cognitive impairment, mood disorders, and schizophrenia. Further studies are necessary to confirm ω-3 fatty acids' supplementation as a potential rational treatment in psychiatric disorders.

Docosahexanoic acid (DHA) and arachidonic acid (ARA) are long chain essential fatty acids used as supplements in commercial infant formula. DHA/ARA deficient states are associated with adverse neurological outcomes in animals and humans. Preterm infants are at risk for DHA/ARA deficiency. A few clinical reports on the effects of fatty acid supplementation have shown benefit in preterm, low birth weight, and normal infants in the first year of life, whereas others did not. Studies in animals have reported shortened gestation, fetal growth retardation, reduced infant body mass, and increased fetal mortality with consumption of fatty acids during pregnancy. To understand the data that support fatty acid supplementation in infant formula, a review of the animal model literature was undertaken, to examine the effects of DHA/ARA on neurodevelopment, including the effects on visual acuity. Several points emerged from this review. (1) Animal studies indicate that requirements for DHA/ARA vary depending on developmental age. Alterations of the ratio of DHA/ARA can impact developmental outcome. (2) The available studies suggest that while supplementation of DHA/ARA in an appropriate ratio can increase tissue levels of these fatty acids in the brain and retina, tissues sensitive to depletion of fatty acids, the benefit of routine supplementation remains unclear. Few studies measure functional outcome relative to changes in physiologic pools of DHA/ARA after supplementation. (3) Animal literature does not support a clear long-term benefit of replenishing DHA/ARA tissue levels and administration of these fatty acids at concentrations above those in human milk suggests adverse effects on growth, survival, and neurodevelopment., (© 2011 Wiley-Liss, Inc.)

Objective: To evaluate the effectiveness and safety of polyunsaturated fatty acids for the treatment of the premenstrual syndrome (PMS) using a graded symptom scale and to assess the effect of this treatment on basal plasma levels of prolactin and total cholesterol., Methods: A randomized, double-blind, placebo-controlled study was conducted with 120 women with PMS divided into three groups and treated with 1 or 2 grams of the medication or placebo. Symptoms were recorded over a 6-month period using the Prospective Record of the Impact and Severity of Menstruation (PRISM) calendar. Total cholesterol and prolactin levels were measured. Analysis of variance (ANOVA), Pearson's chi-square test, Wilcoxon's nonparametric signed-rank test for paired samples and the Mann-Whitney nonparametric test for independent samples were used in the statistical analysis., Results: There were no differences in age, marital status, schooling or ethnicity between the groups. In the group treated with 1 gram of the medication, a significant reduction was found when the median PRISM score recorded in the luteal phase at baseline (99) was compared with the median score recorded in the 3rd month (58) and in the 6th month of evaluation (35). In the 2-gram group, these differences were even more significant (baseline score: 98; 3rd month: 48; 6th month: 28). In the placebo group, there was a significant reduction at the 3rd but not at the 6th month (baseline: 96.5; 3rd month: 63.5; 6th month: 62). The difference between the phases of the menstrual cycle was greater in the 2-gram group compared to the group treated with 1 gram of the medication. There were no statistically significant differences in prolactin or total cholesterol levels between baseline values and those recorded after six months of treatment., Conclusion: The difference between the groups using the medication and the placebo group with respect to the improvement in symptomatology appears to indicate the effectiveness of the drug. Improvement in symptoms was higher when the 2-gram dose was used. This medication was not associated with any changes in prolactin or total cholesterol levels in these women.

The 9th Unilever Nutrition Symposium entitled 'Essential fats for future health', held on 26-27 May 2010, aimed to review the dietary recommendations for essential fatty acids (EFA); discuss the scientific evidence for the roles of EFA in cognition, immune function and cardiovascular health; and to identify opportunities for joint efforts by industry, academia, governmental and non-governmental organizations to effectively improve health behaviour. This paper summarizes the main conclusions of the presentations given at the symposium. Linoleic acid (LA) and α-linolenic acid (ALA) are EFA that cannot by synthesized by the human body. Docosahexaenoic acid (DHA) is considered as conditionally essential because of its limited formation from ALA in the human body and its critical role in early normal retinal and brain development and, jointly with eicosapentaenoic acid (EPA), in prevention of cardiovascular disease (CVD). Some evidence for possible beneficial roles of n-3 fatty acids for immune function and adult cognitive function is emerging. A higher consumption of polyunsaturated fatty acids (PUFA; >10%E), including LA, ALA and at least 250-500 mg per day of EPA+DHA, is recommended for prevention of coronary heart disease (CHD). Two dietary interventions suggest that EFA may affect CVD risk factors in children similarly as in adults. To ensure an adequate EFA intake of the population, including children, public health authorities should develop clear messages based on current science; ensure availability of healthy, palatable foods; and collaborate with scientists, the food industry, schools, hospitals, health-care providers and communities to encourage consumers to make healthy choices.

Polyunsaturated fatty acids are important membrane components that influence membrane integrity and fluidity. In the present study, the effect of oral supplementation for 60 days with essential fatty acids (omega 3, 6 and 9) and vitamin E on canine semen quality was evaluated. Sixteen dogs were selected for the experiment; eight were used as the control group and eight received the fatty acid supplemented diet for 60 days. Semen samples were taken every 15 days during the entire experimental period and were analyzed for volume (ml), motility (%), vigour (0-5), concentration (x10(6)/ml), morphology of spermatozoa (%), plasma membrane integrity (%; using the hyposmotic swelling test) and thermoresistance (motility and vigour after 4 h at 38 degrees C). We concluded that, daily supplementation with omega 3, omega 6 and omega 9 fatty acids, together with vitamin E, for a period of 60 days, significantly increased the semen volume of the treated group after 15 days of supplementation; the vigour and concentration of spermatozoa were superior after the first month of supplementation, while the percentage of morphologically abnormal spermatozoa decreased and the cells were protected against thermal stress.

Aging results in the development of cognitive and motor deficits in humans and animals that are evident by midlife. These deficits are thought to stem from neuronal damage and dysfunction as a result of a variety of stressors, including increased oxidative stress and modifications in brain lipid composition. Recent clinical and animal studies have identified nutritional intervention as a viable method to curtail the cognitive aging process. Human studies have been primarily observational and have indicated that inclusion of antioxidant-rich foods in the diet can slow the progression of cognitive decline. Basic science studies investigating nutritional modulation of age-related cognitive decline have focused on foods rich in antioxidants or essential fatty acids. The purpose of this review is to discuss recent advancements in animal research showing that age-related cognitive and behavioral decline can be ameliorated with nutritional supplementation with polyphenol- or polyunsaturated fatty acid-rich plant foods.

Background: In alternative and complementary medicine, the use of essential and fatty oils has become more and more popular. In addition to conventional medical therapies, self-medication is showing increasing popularity, using agents with unclear compounds and poorly controlled dosages. Among other disorders, these alternative treatments are used in bronchitis and rhinitis, including some topical applications. Thus, the influence on ciliated epithelia should be evaluated, because a disturbance of the ciliary function can lead to recurrent sinusitis and chronic rhinosinusitis. The aim of this study was to test the influence of fatty and essential oils on the ciliary beat frequency (CBF) of nasal mucosa in vivo., Methods: The influence of sesame oil, soy oil, peanut oil, Miglyol 840, thyme oil, lavender oil, eucalyptus oil, and menthol on the ciliary activity of nasal brushings was evaluated by digital high-speed imaging., Results: The presence of most fatty oils resulted in an increase in CBF, the effect being highest for peanut oil. Miglyol 840 had no significant influence on CBF. The essential oils were tested at a concentration of 0.2 and 2%. Thyme oil did not affect CBF, whereas the presence of all other essentials oils resulted in an increase in CBF; the effect was higher at 0.2% than at 2%., Conclusion: Except thyme oil and Miglyol 840, all tested oils caused an increase in CBF. Interestingly, the 0.2% concentrations of essential oils resulted in stronger effects when compared with the 2% concentrations.

Background: Oxidative stress is implicated in the development of a range of neurological diseases. There is increasing interest in the neuroprotective efficacy of antioxidants in modulating such processes with at least one polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial effects of adjunctive n-3 polyunsaturated fatty acids with combined intakes of vitamin C and E on both the positive and negative symptoms of schizophrenia have been reported. Robust in vitro systems are desirable, enabling a mechanistic investigation of the molecular mechanisms underpinning such effects and identification of further potentially efficacious nutraceuticals., Materials and Method: A comparative study employing a human lymphoblastoid cell line derived from a subject with early onset schizophrenia, a neuroblastoma IMR-32 cell line and the histiocytic lymphoma U937 cell line was undertaken. The cytoprotective effects of two phenols in affording protection to cellular DNA from an oxidative challenge were assessed in untreated and fatty acid treated cell lines., Results and Conclusion: Marked differences in the uptake of fatty acids by the cell types were found and the IMR-32 cell line was most susceptible to the oxidant challenge. Hydroxytyrosol gave significant cytoprotection in all three-cell lines and this possible neuroprotective efficacy warrants further investigation, both in vitro and in vivo.

Dry eye disease is a common and increasingly prevalent condition particularly associated with advancing age and postmenopausal women. Epidemiological studies identify prevalence rates ranging from 7% in the US to 33% in the Asian population. Research increasingly identifies risk factors of increasing age, female sex, smoking, use of video display terminals and use of certain medications as well as environmental stresses as aggravating factors for the disease. Basic and clinical investigations provide cumulative evidence of hyperosmolarity of the tear film and ocular surface/lacrimal gland inflammation as pathogenic features of dry eye disease. A decline in systemic and local levels of sex hormones is associated with advancing age and advancing disease. Pharmacological therapeutic interventions include enhanced lubricants and anti-inflammatory drugs such as topical corticosteroids and ciclosporin (cyclosporine A). Secretagogues and hormonal supplementation are potential future therapies. The increased understanding of the contributing and pathogenetic factors responsible for dry eye provides a rationale for multiple therapeutic options for this multi-factorial disease. In the elderly patient it is important to recognize the physical and cognitive limitations that will influence the selection of appropriate topical medication.

The aim of this study was to examine the neurotoxicity of formaldehyde on prefrontal cortex and the protective effects of omega-3 essential fatty acids against these toxic effects. For this purpose, 21 male Wistar rats were divided into three groups. The rats in group I comprised the controls, while the rats in group II were injected every other day with formaldehyde (FA). The rats in group III received omega-3 fatty acids daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation. The brains of the rats were removed and the prefrontal cortex tissues were obtained from all brain specimens. Some of the prefrontal cortex tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The remaining prefrontal cortex tissue specimens were used for light microscopic and immunohistochemical evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with formaldehyde compared with those of the controls. Furthermore, in the microscopic examination of this group, formation of apoptotic bodies, pycnotic cells, and apoptotic cells including nuclear fragmentation and membrane budding were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to formaldehyde. Additionally, cellular damage caused by formaldehyde was decreased, and structural appearance was similar to that of the control rats in this group. The biochemical and histological findings observed in all groups were also confirmed by immunohistochemical evaluation. It was determined that formaldehyde-induced neuronal damage in prefrontal cortex was prevented by administration of omega-3 essential fatty acids., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD). Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results. This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.

Aim: To compare the composition of fatty acids (FAs) in diet, and the expression of delta-6 desaturase (D6D) and delta-5 desaturase (D5D) genes in peripheral blood mononuclear cells (PBMCs) between Chinese and Europeans., Methods: Three-day dietary records from 20 subjects from Beijing, China (n = 10) and Kent, UK (n = 10) were analysed. Expression of PBMC D6D and D5D genes of the subjects was determined using RT-PCR., Results: The dietary intake of Chinese subjects contained less saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), but more essential fatty acids (EFAs) than that of Europeans. Levels of expression of PBMC D6D and D5D genes of Chinese subjects were significantly lower than those of Europeans. A significant positive correlation was found between dietary intake of total SFAs and total MUFAs and expression of PBMC D6D and D5D genes, but a significant negative correlation between dietary intake of linoleic acid (LA) and alpha-linolenic acid (LNA) and the expression of PBMC D6D and D5D genes., Conclusion: Intake of high SFAs and MUFAs appears to increase expression of PBMC D6D and D5D genes, whilst high EFAs intake appears to decrease expression of PBMC D6D and D5D genes. A follow-up study of the expression of D6D and D5D genes in Chinese who live in European countries with high SFA and MUFA diets would be of interest., (Copyright 2006 S. Karger AG, Basel.)

This study was conducted to investigate the influence of supplemented evening primrose oil (EPO) on osteoclast expression during experimental tooth movement in rats. Forty-eight 10-week-old male Sprague-Dawley rats were divided into experimental and control groups. Animals in the experiment group were fed a 7.25 g/kg daily dose of EPO orally by gastric intubation for 20 days before orthodontic tooth movement. The animals in the control group received an equivalent volume of distilled water by the same method. On day 21, a 40-g mesial tipping force was applied to the maxillary right first molar of each rat. After loading, six animals in each group were sacrificed on days 0, 3, 7, and 14 with the appliance in situ. On day 3, the number of osteoclasts on the appliance side of the experimental group was significantly increased compared with the control group (P < .05). On day 7, the number of osteoclasts on the non-appliance side of the experimental group was significantly increased compared with the control group (P < .05). This study indicates that oral administration of EPO can increase the number of osteoclasts and may accelerate orthodontic tooth movement.

Our aim was to determine the effect of n-3 (2%, wt/wt, fish oil rich diet) and n-6 (2%, wt/wt, evening primrose oil rich diet) fatty acid dietary supplementation and their combination with two concentrations of vitamin E (40 vs 200 mg/kg) on semen variables and on fatty acid and vitamin E profiles of spermatozoa in broiler breeders at 32, 42 and 52 weeks of age. The inclusion of fish oil in the cockerel diets increased the docosahexaenoic acid proportion in the sperm phospholipid fraction, which was almost threefold higher compared to the other two groups irrespective of vitamin E supplementation. In contrast, an increase in the proportion of total n-6 polyunsaturates, mainly 22:4n-6, was observed in the evening primrose oil group compared to the control only when the dietary content of vitamin E was increased to 200 mg/kg. Sperm concentration was decreased in the fish and evening primrose oil groups if vitamin E was 40 mg/kg, but such an effect was prevented in the fish, not the evening primrose oil group, by increasing the vitamin E to 200 mg. The proportion of motile spermatozoa was improved by the increased supplementation of vitamin E in all oil treatments.

Biochemical evidence of essential fatty acid deficiency (EFAD) may exist in protein-energy malnutrition (PEM). EFAD is characterised by low 18:2omega6, often in combination with low 20:4omega6 and 22:6omega3, and high 18:1omega9 and 20:3omega9. Some PEM symptoms, notably skin changes, impaired resistance to infections, impaired growth rate and disturbed development may at least partly be explained by EFAD. One or more of the following factors could induce EFAD in PEM: low EFA intake, poor lipid digestion, absorption, transport, desaturation and increased EFA beta-oxidation and peroxidation. EFAD may perpetuate itself by decreasing lipid absorption and transport, and aggravate PEM by impairing nutrient absorption and dietary calorie utilisation. Micronutrient deficiencies may contribute to the impaired EFA bioavailability and metabolism. Nutritional rehabilitation strategies in PEM may consider adequate intakes of EFA and micronutrients, e.g. by promoting breastfeeding. More research is required to gain detailed insight into the role of EFAD in PEM.