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1
Liin, Sara I., Malin Silverå Ejneby, Rene Barro-Soria, Mark Alexander Skarsfeldt, Johan E. Larsson, Frida Starck Härlin, Teija Parkkari, et al. "Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel." Proceedings of the National Academy of Sciences 112, no. 18 (April 21, 2015): 5714–19. http://dx.doi.org/10.1073/pnas.1503488112.
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Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.
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Szymczak, Melissa, Michael Murray, and Nenad Petrovic. "Modulation of angiogenesis by ω-3 polyunsaturated fatty acids is mediated by cyclooxygenases." Blood 111, no. 7 (April 1, 2008): 3514–21. http://dx.doi.org/10.1182/blood-2007-08-109934.
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Abstract The potential role of dietary fats in cancer is attracting considerable interest within the community. Both epidemiologic and experimental findings suggest that omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are almost absent from typical Western diets, exert protective effects against cancer progression, although the precise mechanism of this suppression remains unknown. One of the potential targets for ω-3 PUFAs in cancer suppression is angiogenesis, a process of new blood vessel formation within rapidly growing tumors. Here, we demonstrate that ω-6 PUFAs stimulate and ω-3 PUFAs inhibit major proangiogenic processes in human endothelial cells, including the induction of angiopoietin-2 (Ang2) and matrix metalloprotease-9, endothelial invasion, and tube formation, that are usually activated by the major ω-6 PUFA arachidonic acid. The cyclooxygenase (COX)–mediated conversion of PUFAs to prostanoid derivatives participated in modulation of the expression of Ang2. Thus, the ω-6 PUFA–derived prostaglandin E2 augmented, whereas the ω-3 PUFA–derived prostaglandin E3 suppressed the induction of Ang2 by growth factors. Our findings are consistent with the suggestion that PUFAs undergo biotransformation by COX-2 to lipid mediators that modulate tumor angiogenesis, which provides new insight into the beneficial effects of ω-3 PUFAs.
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Song, Lishuang, Lei Yang, Jiapeng Wang, Xuefei Liu, Lige Bai, Anqi Di, and Guangpeng Li. "Generation of Fad2 and Fad3 transgenic mice that produce n-6 and n-3 polyunsaturated fatty acids." Open Biology 9, no. 10 (October 2019): 190140. http://dx.doi.org/10.1098/rsob.190140.
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Linoleic acid (18 : 2, n-6) and α-linolenic acid (18 : 3, n-3) are polyunsaturated fatty acids (PUFAs), which are essential for mammalian health, development and growth. However, the majority of mammals, including humans, are incapable of synthesizing n-6 and n-3 PUFAs. Mammals must obtain n-6 and n-3 PUFAs from their diet. Fatty acid desaturase (Fad) plays a critical role in plant PUFA biosynthesis. Therefore, we generated plant-derived Fad3 single and Fad2–Fad3 double transgenic mice. Compared with wild-type mice, we found that PUFA levels were greatly increased in the single and double transgenic mice by measuring PUFA levels. Moreover, the concentration of n-6 and n-3 PUFAs in the Fad2–Fad3 double transgenic mice were greater than in the Fad3 single transgenic mice. These results demonstrate that the plant-derived Fad2 and Fad3 genes can be expressed in mammals. To clarify the mechanism for Fad2 and Fad3 genes in transgenic mice, we measured the PUFAs synthesis-related genes. Compared with wild-type mice, these Fad transgenic mice have their own n-3 and n-6 PUFAs biosynthetic pathways. Thus, we have established a simple and efficient method for in vivo synthesis of PUFAs.
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Kirkup, S. E., Z. Cheng, M. Elmes, D. C. Wathes, and D. R. E. Abayasekara. "Polyunsaturated fatty acids modulate prostaglandin synthesis by ovine amnion cells in vitro." REPRODUCTION 140, no. 6 (December 2010): 943–51. http://dx.doi.org/10.1530/rep-09-0575.
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Diets or supplements high in n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to influence the timing of parturition. PUFAs are substrates for prostaglandin (PG) synthesis, and PGs play central roles in parturition. Hence, the effects of altering PUFA composition may be mediated through alterations in the type and relative quantities of PGs synthesised. Therefore, we have investigated the effects of a range of n-3 and n-6 PUFAsin vitroon PG synthesis by amnion cells of late gestation ewes. The n-6 PUFA, arachidonic acid (20:4, n-6), increased synthesis of two-series PGs. Degree of stimulation induced by the n-6 PUFAs was dependent on the position of the PUFA in the PG synthetic pathway, i.e. PG production of the two-series (principally prostaglandin E2:PGE2) increased progressively with longer chain PUFAs. Effects of n-3 PUFAs on output of PGE2were more modest and variable. The two shorter chain n-3 PUFAs, α-linolenic acid (18:3, n-3) and stearidonic acid (18:4, n-3), induced a small but significant increase in PGE2output, while the longest chain n-3 PUFA docosahexaenoic acid (22:6, n-3) inhibited PGE2synthesis. Dihomo-γ-linolenic acid (20:3, n-6), the PUFA substrate for synthesis of one-series PGs, induced an increase in PGE1generation and a decrease in PGE2and PGE3outputs. Hence, we have demonstrated that PUFA supplementation of ovine amnion cellsin vitroaffects the type and quantity of PGs synthesised.
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González-Rodríguez, Liliana G., Aránzazu Aparicio, Ana M. López-Sobaler, and Rosa M. Ortega. "Omega 3 and Omega 6 Fatty Acids Intake and Dietary Sources in a Representative Sample of Spanish Adults." International Journal for Vitamin and Nutrition Research 83, no. 1 (February 1, 2013): 36–47. http://dx.doi.org/10.1024/0300-9831/a000143.
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The present study analyzes the intake of omega 3 (n-3 PUFAs) and omega 6 (n-6 PUFAs) and dietary sources in a representative sample of Spanish adults. For this purpose 418 adults (18 - 60 y), from 15 Spanish provinces were studied. The intake of energy and nutrients [specifically, the n-3 polyunsaturated fatty acids (PUFAs,) α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA); and the n-6 PUFA, linoleic acid (LA)] was determined using a 24-hour recall questionnaire for two days. The Multiple Source Method (MSM) was used to estimate participants usual fatty acid intake. The total n-3 PUFAs intake was 1.8 ± 0.60 g/day (ALA: 1.3 ± 0.32, EPA: 0.16 ± 0.14, and DHA: 0.33 ± 0.21 g/day) and n-6 PUFA intake was 11.0 ± 2.7 g/day (LA: 10.8 ± 2.7 g/day). A high proportion of participants did not meet their nutrient intake goals for total n-3 PUFAs (84.7 %), ALA (45.0 %), and EPA plus DHA (62.9 %). The main food sources for ALA were oil, dairy products, and meat; for EPA fish; for DHA, fish, eggs, and meat; and for LA, oils, meat, and cereals. Therefore, an increase in the intake of foods rich in n-3 PUFAs or the use of supplements with n-3 PUFAs might help to improve the n-3 PUFA intake.
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Park, Yongsoon, Yoo-Sin Park, Seok Hyeon Kim, Dong Hoon Oh, and Yong-Chon Park. "Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea." Annals of Nutrition and Metabolism 66, no. 2-3 (2015): 141–48. http://dx.doi.org/10.1159/000377640.
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Background: Controversy over the efficacy of n-3 polyunsaturated fatty acids (PUFAs) in depression continues to this day. The present study investigated the hypothesis that n-3 PUFA supplementation reduces depressive symptoms in Korean patients with major depressive disorder. Methods: In a randomized, double-blind, placebo-controlled, 12-week, parallel-group trial, 35 patients with Center for Epidemiological Studies Depression Scale Korean version (CES-D-K) scores ≥25 and depression confirmed by a psychiatrist were assigned to take either 3 capsules of n-3 PUFAs (1,140 mg of EPA + 600 mg of DHA; n = 18) or placebo (olive oil + safflower oil; n = 17). Results: Supplementation with n-3 PUFAs significantly reduced Clinical Global Impression Improvement (CGI-I) scores as compared with intake of placebo using intention-to-treat analysis with last-observation-carried-forward after adjusting for energy, fat, and fish intake. However, the CES-D-K, Hamilton Depression Rating Scale-17, and Clinical Global Impression Scale scores did not significantly differ between the n-3 PUFA and placebo groups. After supplementation with n-3 PUFAs, the erythrocyte levels of n-3 PUFAs were significantly increased, but n-6 PUFA levels were decreased. Conclusions: n-3 PUFAs demonstrated an advantage over placebo that did not reach clinical significance, although CGI-I score was significantly decreased in the n-3 PUFA group as compared with the placebo group.
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Chen, Liping, Naoki Takatani, Fumiaki Beppu, Kazuo Miyashita, and Masashi Hosokawa. "The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-Ay Mice." Nutrients 11, no. 12 (November 22, 2019): 2866. http://dx.doi.org/10.3390/nu11122866.
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n-3 Polyunsaturated fatty acid binding phospholipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-Ay mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-Ay mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic lipid content was markedly alleviated depending on the neutral lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a functional lipid for reducing serum and liver lipids and is able to supply n-3 PUFAs to KK-Ay mice.
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Kim, Youngyo, and Jeongseon Kim. "N-6 Polyunsaturated Fatty Acids and Risk of Cancer: Accumulating Evidence from Prospective Studies." Nutrients 12, no. 9 (August 20, 2020): 2523. http://dx.doi.org/10.3390/nu12092523.
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Previous studies on the association between polyunsaturated fatty acids (PUFAs) and cancer have focused on n-3 PUFAs. To investigate the association between intake or blood levels of n-6 PUFAs and cancer, we searched the PubMed and Embase databases up to March 2020 and conducted a meta-analysis. A total of 70 articles were identified. High blood levels of n-6 PUFAs were associated with an 8% lower risk of all cancers (relative risk (RR) = 0.92; 95% confidence interval (CI): 0.86–0.98) compared to low blood levels of n-6 PUFAs. In the subgroup analyses by cancer site, type of n-6 PUFAs, and sex, the inverse associations were strong for breast cancer (RR = 0.87; 95% CI: 0.77–0.98), linoleic acid (LA) (RR = 0.91; 95% CI: 0.82–1.00), and women (RR = 0.88; 95% CI: 0.79–0.97). In the dose-response analysis, a 2% and 3% decrease in the risk of cancer was observed with a 5% increase in blood levels of n-6 PUFAs and LA, respectively. Thus, there was no significant association between n-6 PUFA intake and the risk of cancer. The pooled RR of cancer for the highest versus lowest category of n-6 PUFA intake was 1.02 (95% CI: 0.99–1.05). Evidence from prospective studies indicated that intake of n-6 PUFAs was not significantly associated with risk of cancer, but blood levels of n-6 PUFAs were inversely associated with risk of cancer.
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Ruf, Thomas, and Walter Arnold. "Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 294, no. 3 (March 2008): R1044—R1052. http://dx.doi.org/10.1152/ajpregu.00688.2007.
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Polyunsaturated fatty acids (PUFAs) can have strong effects on hibernation and daily torpor in mammals. High dietary PUFA contents were found to increase proneness for torpor, decrease body temperatures, prolong torpor bout duration, and attenuate hibernation mass loss. The mechanism by which PUFAs enhance torpor and hibernation is unknown, however. On the basis of a review of the literature, and on reexamining our own data on alpine marmots, we propose that effects on hibernation are not due to PUFAs in general, but to shifts in the ratio of n-6 PUFAs to n-3 PUFAs in membrane phospholipids. Specifically, high ratios of n-6 to n-3 PUFAs increase the activity of the Ca2+-Mg2+ pump in the sarcoplasmic reticulum of the heart (SERCA) and counteract Q10 effects on SERCA activity at low tissue temperatures. Therefore, high n-6 to n-3 PUFA ratios in cardiac myocyte membranes appear to protect the hibernating heart from arrhythmia, which in hypothermic nonhibernators is caused by massive increases in cytosolic Ca2+. The resulting reduced risk of cardiac arrest during hypothermia may explain why increased dietary uptake of n-6 PUFAs, but not of n-3 PUFAs, can strongly enhance the propensity for hibernation, and allows heterotherms to reach lower body temperatures, with associated increased energy savings. Therefore, at least for herbivorous hibernators, such as marmots, linoleic acid (C18:2 n-6)—the dietary source of all n-6 PUFAs—appears to represent a crucial and limited resource in natural environments.
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Wang, Xiaofeng, and Marianna Kulka. "n-3 polyunsaturated fatty acids (PUFAs) inhibit mast cell activation by disrupting FcεRI association with lipid rafts (HYP3P.401)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 54.13. http://dx.doi.org/10.4049/jimmunol.192.supp.54.13.
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Abstract INTRODUCTION: n-3 PUFAs can suppress allergic inflammation. We hypothesized that n-3 PUFAs inhibit mast cell (MC) activation through modification of FcεRI association with lipid rafts on plasma membrane. METHODS: Bone marrow-derived MCs (BMMC) were cultivated from C57BL/6 wild-type (WT) and fat-1 transgenic mice which express fatty acid n-3 desaturase and produce endogenous n-3 PUFAs. Exogenous n-3 PUFAs were supplemented to WT BMMC. Degranulation, cysteinyl leukotriene (cys-LT), and tumor necrosis factor (TNF) and chemokine (C-C motif) ligand 2 (CCL2) release were evaluated following FcεRI activation. Lipid rafts were isolated by sucrose gradient centrifugation. FcεRI expression was determined by flow cytometry and western blot analysis. RESULTS: Gas chromatography-mass spectrometry analysis showed increased n-3 PUFA levels in whole cell lysates and lipid raft fractions of fat-1 BMMC compared to WT BMMC and in whole cell lysates of PUFA-supplemented BMMC. n-3 PUFAs inhibited degranulation and cys-LT, TNF and CCL2 production compared to untreated BMMC. n-3 PUFAs did not alter expression of surface or total cell FcεRI. However, n-3 PUFAs suppressed FcεRI localization in lipid rafts of unstimulated cells, and disrupted FcεRI shuttling to rafts in stimulated BMMC. CONCLUSIONS: Our results suggest that n-3 PUFAs inhibit MC activation by disruption of FcεRI localization and shuttling into lipid rafts.
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Kyriakaki, Panagiota, Foivos Zisis, Athanasios C. Pappas, Alexandros Mavrommatis, and Eleni Tsiplakou. "Effects of PUFA-Rich Dietary Strategies on Ruminants’ Mammary Gland Gene Network: A Nutrigenomics Review." Metabolites 13, no. 1 (December 27, 2022): 44. http://dx.doi.org/10.3390/metabo13010044.
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Although the inclusion of polyunsaturated fatty acids (PUFAs) in ruminants’ diets appears to be a well-documented strategy to enrich milk with PUFAs, several gene networks that regulate milk synthesis and mammary gland homeostasis could be impaired. The objective of this literature review is to assess the effects of nutritional strategies focused on enriching milk with PUFAs on gene networks regulating mammary gland function and lipogenesis, as well as the impact of feed additives and bioactive compounds with prominent antioxidant potential on immune-oxidative transcriptional profiling, as a part of mammary gland homeostasis and health. The findings support the conclusion that PUFAs’ inclusion in ruminants’ diets more strongly downregulate the stearoyl-CoA desaturase (SCD) gene compared to other key genes involved in de novo fatty acid synthesis in the mammary gland. Additionally, it was revealed that seed oils rich in linoleic and linolenic acids have no such strong impact on networks that regulate lipogenic homeostasis compared to marine oils rich in eicosapentaenoic and docosahexaenoic acids. Furthermore, ample evidence supports that cows and sheep are more prone to the suppression of lipogenesis pathways compared to goats under the impact of dietary marine PUFAs. On the other hand, the inclusion of feed additives and bioactive compounds with prominent antioxidant potential in ruminants’ diets can strengthen mammary gland immune-oxidative status. Considering that PUFA’s high propensity to oxidation can induce a cascade of pro-oxidant incidences, the simultaneous supplementation of antioxidant compounds and especially polyphenols may alleviate any side effects caused by PUFA overload in the mammary gland. In conclusion, future studies should deeply investigate the effects of PUFAs on mammary gland gene networks in an effort to holistically understand their impact on both milk fat depression syndrome and homeostatic disturbance.
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Anderson, Ethan J., Kathleen Thayne, Mitchel Harris, Kristen Carraway, and Saame Raza Shaikh. "Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany functional adaptations in cardiac mitochondria from mice fed n−3 polyunsaturated fatty acids." Biochemical Journal 441, no. 1 (December 14, 2011): 359–66. http://dx.doi.org/10.1042/bj20110626.
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Diets replete with n−3 PUFAs (polyunsaturated fatty acids) are known to have therapeutic potential for the heart, although a specifically defined duration of the n−3 PUFA diet required to achieve these effects remains unknown, as does their mechanism of action. The present study was undertaken to establish whether adaptations in mitochondrial function and stress tolerance in the heart is evident following short- (3 weeks) and long- (14 weeks) term dietary intervention of n−3 PUFAs, and to identify novel mechanisms by which these adaptations occur. Mitochondrial respiration [mO2 (mitochondrial O2)], H2O2 emission [mH2O2 (mitochondrial H2O2)] and Ca2+-retention capacity [mCa2+ (mitochondrial Ca2+)] were assessed in mouse hearts following dietary intervention. Mice fed n−3 PUFAs for 14 weeks showed significantly lower mH2O2 and greater mCa2+ compared with all other groups. However, no significant differences were observed after 3 weeks of the n−3 PUFA diet, or in mice fed on an HFC (high-fat control) diet enriched with vegetable shortening, containing almost no n−3 PUFAs, for 14 weeks. Interestingly, expression and activity of key enzymes involved in antioxidant and phase II detoxification pathways, all mediated by Nrf2 (nuclear factor E2-related factor 2), were elevated in hearts from mice fed the n−3 PUFA diet, but not hearts from mice fed the HFC diet, even at 3 weeks. This increase in antioxidant systems in hearts from mice fed the n−3 PUFA diet was paralleled by increased levels of 4-hydroxyhexenal protein adducts, an aldehyde formed from peroxidation of n−3 PUFAs. The findings of the present study demonstrate distinct time-dependent effects of n−3 PUFAs on mitochondrial function and antioxidant response systems in the heart. In addition, they are the first to provide direct evidence that non-enzymatic oxidation products of n−3 PUFAs may be driving mitochondrial and redox-mediated adaptations, thereby revealing a novel mechanism for n−3 PUFA action in the heart.
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Šmíd, Václav, Karel Dvořák, Kamila Stehnová, Hynek Strnad, Josep Rubert, Jan Stříteský, Barbora Staňková, et al. "The Ameliorating Effects of n-3 Polyunsaturated Fatty Acids on Liver Steatosis Induced by a High-Fat Methionine Choline-Deficient Diet in Mice." International Journal of Molecular Sciences 24, no. 24 (December 7, 2023): 17226. http://dx.doi.org/10.3390/ijms242417226.
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The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.
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Ćurić, Željka Breškić, Ana Marija Masle, Aleksandar Kibel, Kristina Selthofer-Relatić, Ana Stupin, Zrinka Mihaljević, Ivana Jukić, et al. "Effects of n-3 Polyunsaturated Fatty Acid-Enriched Hen Egg Consumption on the Inflammatory Biomarkers and Microvascular Function in Patients with Acute and Chronic Coronary Syndrome—A Randomized Study." Biology 10, no. 8 (August 14, 2021): 774. http://dx.doi.org/10.3390/biology10080774.
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This study aimed to test the effect of n-3 polyunsaturated fatty acid (PUFA)-enriched hen egg consumption on serum lipid and free fatty acid profiles, inflammatory and oxidative stress biomarkers, and microvascular reactivity in patients with coronary artery disease (CAD). Forty CAD patients participated in this study. Of those, 20 patients had acute CAD (Ac-CAD), and 20 patients had chronic CAD (Ch-CAD). The control group (N = 20) consumed three regular hen eggs/daily (249 mg n-3 PUFAs/day), and the n-3 PUFAs group (N = 20) consumed three n-3 PUFA-enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Serum n-3 PUFA concentration significantly increased (in all CAD patients), while LDL cholesterol and IL-6 (in Ac-CAD patients), and hsCRP and IL-1a (in all CAD patients) significantly decreased in the n-3 PUFAs group. Glutathione peroxidase (GPx) activity significantly decreased, and forearm skin microvascular reactivity in response to vascular occlusion (postocclusive reactive hyperemia (PORH)) remained unchanged in both the n-3 PUFAs and control groups in total CAD, Ac-CAD, and Ch-CAD patients. Potentially, n-3 PUFA-enriched hen eggs can change the free fatty acid profile to a more favorable lower n6/n3 ratio, and to exhibit mild anti-inflammatory effects but not to affect microvascular reactivity in CAD patients.
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Tu, Maolin, Weicang Wang, Guodong Zhang, and Bruce D. Hammock. "ω-3 Polyunsaturated Fatty Acids on Colonic Inflammation and Colon Cancer: Roles of Lipid-Metabolizing Enzymes Involved." Nutrients 12, no. 11 (October 28, 2020): 3301. http://dx.doi.org/10.3390/nu12113301.
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Substantial human and animal studies support the beneficial effects of ω-3 polyunsaturated fatty acids (PUFAs) on colonic inflammation and colorectal cancer (CRC). However, there are inconsistent results, which have shown that ω-3 PUFAs have no effect or even detrimental effects, making it difficult to effectively implement ω-3 PUFAs for disease prevention. A better understanding of the molecular mechanisms for the anti-inflammatory and anticancer effects of ω-3 PUFAs will help to clarify their potential health-promoting effects, provide a scientific base for cautions for their use, and establish dietary recommendations. In this review, we summarize recent studies of ω-3 PUFAs on colonic inflammation and CRC and discuss the potential roles of ω-3 PUFA-metabolizing enzymes, notably the cytochrome P450 monooxygenases, in mediating the actions of ω-3 PUFAs.
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Pærregaard, Simone Isling, Marianne Agerholm, Annette Karen Serup, Tao Ma, Bente Kiens, Lise Madsen, Karsten Kristiansen, and Benjamin Anderschou Holbech Jensen. "FFAR4 (GPR120) Signaling Is Not Required for Anti-Inflammatory and Insulin-Sensitizing Effects of Omega-3 Fatty Acids." Mediators of Inflammation 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/1536047.
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Free fatty acid receptor-4 (FFAR4), also known as GPR120, has been reported to mediate the beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) by inducing an anti-inflammatory immune response. Thus, activation of FFAR4 has been reported to ameliorate chronic low-grade inflammation and insulin resistance accompanying obesity. However, conflicting reports on the role of FFAR4 in mediating the effects ofω3-PUFAs are emerging, suggesting that FFAR4 may not be the sole effector. Hence analyses of the importance of this receptor in relation to other signaling pathways and prominent effects ofω3-PUFAs remain to be elucidated. In the present study, we usedFfar4knockouts (KO) and heterozygous (HET) mice fed either low fat, low sucrose reference diet; high fat, high sucroseω3-PUFA; or high fat, high sucroseω6-PUFA diet for 36 weeks. We demonstrate that both KO and HET mice fedω3-PUFAs were protected against obesity, hepatic triacylglycerol accumulation, and whole-body insulin resistance. Moreover,ω3-PUFA fed mice had increased circulating protein levels of the anti-inflammatory adipokine, adiponectin, decreased fasting insulin levels, and decreased mRNA expression of several proinflammatory molecules within visceral adipose tissue. In conclusion, we find that FFAR4 signaling is not required for the reported anti-inflammatory and insulin-sensitizing effects mediated byω3-PUFAs.
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Castillo Salinas, Félix, Alicia Montaner Ramón, Félix-Joel Castillo Ferrer, Adrià Domingo-Carnice, Begoña Cordobilla, and Joan Carles Domingo. "Erythrocyte Membrane Docosahexaenoic Acid (DHA) and Lipid Profile in Preterm Infants at Birth and Over the First Month of Life: A Comparative Study with Infants at Term." Nutrients 14, no. 23 (November 22, 2022): 4956. http://dx.doi.org/10.3390/nu14234956.
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An observational comparative study was designed to assess the fatty acids profile in erythrocyte membrane phospholipids of 30 preterm neonates (<32 weeks gestation) at birth and after 1 month of life versus a convenience sample of 10 infants born at term. The panel of fatty acids included the families and components of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (PUFAs) as well as enzyme activity indexes and fatty acids ratios. At birth, the comparison of fatty acid families between preterm and term neonates showed a significantly higher content of SFAs and n-6 PUFAs, and a significantly lower content of MUFAs and n-3 PUFAs in the preterm group. After 30 days of life, significantly higher levels of n-6 PUFAs and significantly lower levels of n-3 PUFAs among preterm neonates persisted. At 30 days of birth, n-6 PUFA/n-3 PUFA and arachidonic acid (ARA) ARA/DHA remained significantly elevated, and DHA sufficiency index significantly decreased in the preterm group. The pattern of n-3 PUFA deficiency at birth and sustained for the first month of life would support the need of milk banking fortified with DHA and the use of DHA supplementation in breastfeeding mothers.
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Hergenrader, Alexandra, Matthew VanOrmer, Rebecca Slotkowski, Maranda Thompson, Alyssa Freeman, Olivia Paetz, Sarah Sweeney, et al. "Omega-3 Polyunsaturated Fatty Acid Levels in Maternal and Cord Plasma Are Associated with Maternal Socioeconomic Status." Nutrients 15, no. 20 (October 19, 2023): 4432. http://dx.doi.org/10.3390/nu15204432.
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Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) play a crucial role in fetal growth and neurodevelopment, while omega-6 (n-6) PUFAs have been associated with adverse pregnancy outcomes. Previous studies have demonstrated that socioeconomic status (SES) influences dietary intake of n-3 and n-6 PUFAs, but few studies have evaluated the association between maternal and cord plasma biomarkers of PUFAs and socioeconomic markers. An IRB-approved study enrolled mother–infant pairs (n = 55) at the time of delivery. Maternal and cord plasma PUFA concentrations were analyzed using gas chromatography. Markers of SES were obtained from validated surveys and maternal medical records. Mann–Whitney U tests and linear regression models were utilized for statistical analysis. Maternal eicosapentaenoic acid (EPA) (p = 0.02), cord EPA (p = 0.04), and total cord n-3 PUFA concentrations (p = 0.04) were significantly higher in college-educated mothers vs. mothers with less than a college education after adjustment for relevant confounders. Insurance type and household income were not significantly associated with n-3 or n-6 PUFA plasma concentrations after adjustment. Our findings suggest that mothers with lower educational status may be at risk of lower plasma concentrations of n-3 PUFAs at delivery, which could confer increased susceptibility to adverse pregnancy and birth outcomes.
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Carneiro, Luisa Cunha, Erin Jane Williams, João Paulo Elsen Saut, Ricarda Maria dos Santos, and Eneiva Carla Carvalho Celeghini. "The effect of n- 3 polyunsaturated fatty acid supplementation on immune and reproductive parameters in dairy cows." Brazilian Journal of Veterinary Research and Animal Science 58 (July 13, 2021): e175224. http://dx.doi.org/10.11606/issn.1678-4456.bjvras.2021.175224.
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In dairy cattle, supplementation with polyunsaturated fatty acids (PUFAs) is considered to be an important tool to decrease the negative energy balance of periparturient dairy cows and improve the reproductive and immune systems. The most common PUFAs added to ruminant diets are omega 3 (n-3 PUFA) as linolenic acid and omega 6 (n-6 PUFA) as linoleic acid. This paper aims to review the potential effects of n-3 PUFA. We consider the effects of n-3 PUFA on the bovine immune system, especially on immune cells, and on in vivo and in vitro reproductive parameters, emphasizing how n-3 PUFAs act as modulators through one or more molecular mechanisms. The incorporation of n-3 PUFA in the dairy cow diet has positive effects on animal fertility and immunity. Future research on n-3 PUFA should be more explored concerning reproduction and immune function, starting from the investigation of basic biology to their potential for application in the clinical and preventive medicine fields.
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Xiao, Yanan, Yifang Chen, Anne Pietzner, Ulf Elbelt, Zhimin Fan, and Karsten H. Weylandt. "Circulating Omega-3 Polyunsaturated Fatty Acids Levels in Coronary Heart Disease: Pooled Analysis of 36 Observational Studies." Nutrients 16, no. 11 (May 24, 2024): 1610. http://dx.doi.org/10.3390/nu16111610.
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Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. Methods: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to July 30, 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. Results: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. Conclusions: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.
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Ekström, Sandra, Emmanouela Sdona, Susanna Klevebro, Jenny Hallberg, Antonios Georgelis, Inger Kull, Erik Melén, Ulf Risérus, and Anna Bergström. "Dietary intake and plasma concentrations of PUFAs in childhood and adolescence in relation to asthma and lung function up to adulthood." American Journal of Clinical Nutrition 115, no. 3 (December 29, 2021): 886–96. http://dx.doi.org/10.1093/ajcn/nqab427.
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ABSTRACT Background PUFAs may influence the risk of asthma; however, long-term prospective studies including objective biomarkers of PUFA intake are lacking. Objectives The objective was to investigate the role of dietary intake and plasma concentrations of n–3 and n–6 (ω-3 and ω-6) PUFAs in childhood and adolescence for the development of asthma and lung function up to young adulthood. Methods The study included participants from the Swedish prospective birth cohort BAMSE. Dietary intake of PUFAs was calculated from FFQs (n = 1992) and plasma proportions of PUFAs were measured in phospholipids (n = 831). We analyzed the n–3 PUFA α-linolenic acid (ALA; 18:3n–3); the sum of very-long-chain (VLC) n–3 PUFAs: EPA (20:5n–3), DHA (22:6n–3), and docosapentaenoic acid (22:5n–3); and the n–6 PUFAs linoleic acid (LA; 18:2n–6) and arachidonic acid (AA; 20:4n–6). Asthma was assessed by questionnaires at 8, 16, and 24 y and lung function was measured by spirometry at 24 y. Results A high (≥median) self-reported dietary intake of LA at 8 y and AA at 16 y was associated with increased risk of prevalent asthma at 24 y (OR: 1.41; 95% CI: 1.10, 1.82 and OR: 1.32; 95% CI: 1.02, 1.70, respectively). In contrast, plasma proportions of ALA, ∑VLC n–3 PUFAs, and AA at 8 y, as well as LA at 16 y, were inversely associated with prevalent asthma at 24 y (e.g., OR: 0.55; 95% CI: 0.38, 0.81 for ∑VLC n–3 PUFAs). No consistent associations were observed with lung function. Conclusions High dietary intake of certain n–6 PUFAs in childhood or adolescence may be associated with increased risk of asthma up to young adulthood, whereas dietary biomarkers of certain n–3 and n–6 PUFAs in plasma may be associated with decreased risk. Thus, the role of diet compared with altered metabolism of PUFAs needs further investigation to improve dietary preventive strategies for asthma.
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Rehmanji, Mohammed, Ashish Kumar, Asha Arumugam Nesamma, Nida Jamil Khan, Tasneem Fatma, and Pannaga Pavan Jutur. "Elucidation of Functional Genes Associated with Long Chain-Polyunsaturated Fatty Acids (LC-PUFAs) Metabolism in Oleaginous Diatom Phaeodactylum tricornutum." Hydrobiology 1, no. 4 (October 12, 2022): 451–68. http://dx.doi.org/10.3390/hydrobiology1040027.
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Phaeodactylum tricornutum is a marine diatom rich in omega-3 fatty acids, a nutraceutical-relevant product. Long chain-polyunsaturated fatty acids (LC-PUFAs) are crucial dietary components for human development and growth. With the availability of genome information and genetic engineering tools, the productivities of OMEGAs have improved, but the functional and organizational relationship of such protein-encoding genes associated with LC-PUFAs biosynthesis is still not clear. Henceforth, our study highlights the conservation pattern, functionality and interaction of LC-PUFAs protein-encoding genes via in silico analysis. The transcriptome and quantitative PCR analysis demonstrates downregulation of ACS4, ELO6b, PTD5a, and MYB106 genes associated with LC-PUFAs synthesis and upregulation of ECoAH and ACAT1 genes associated with β-oxidation in nitrogen-depleted conditions in P. tricornutum. Phylogenomics studies of LC-PUFAs protein-encoding genes show a highly conserved evolutionary pattern in various microalgal lineages. Further, for elucidating the interaction of LC-PUFA metabolic genes, subcellular networks were predicted and pathway enrichment analysis was performed, providing new insights on the crosstalk between LC-PUFA protein-encoding genes (ELO6, PTD5, ACS, and ACL1), regulatory elements (LEC2, MYB, WIN) and transporters (ABCD1). In conclusion, such extensive functional enrichment analysis will undoubtedly aid in the development of genetically engineered algal strains with enhanced production of biomolecules i.e., LC-PUFAs.
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Marza, E., and G. M. Lesa. "Polyunsaturated fatty acids and neurotransmission in Caenorhabditis elegans." Biochemical Society Transactions 34, no. 1 (January 20, 2006): 77–80. http://dx.doi.org/10.1042/bst0340077.
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Changes in PUFA (polyunsaturated fatty acid) metabolism can cause mental retardation and cognitive impairment. However, it is still unclear why altered levels of PUFAs result in neuronal dysfunction. Recent studies on the nematode Caenorhabditis elegans suggest that PUFA depletion may cause cognitive impairment by compromising communication among neurons. Pharmacological and electrophysiological experiments showed that animals devoid of most PUFAs release abnormally low levels of neurotransmitters. In addition, ultrastructural analysis revealed that synapses in these mutants are severely depleted of synaptic vesicles. The conclusion of these studies is that PUFAs are required to maintain a normal pool of synaptic vesicles at pre-synaptic sites, thus ensuring efficient neurotransmission.
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Börjesson, Sara I., and Fredrik Elinder. "An electrostatic potassium channel opener targeting the final voltage sensor transition." Journal of General Physiology 137, no. 6 (May 30, 2011): 563–77. http://dx.doi.org/10.1085/jgp.201110599.
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Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability.
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Kasprowicz, Deborah, Sangeetha Ravindran Nair, Tom Gonyon, Clare Gerstein, Tim Fulghum, and Phil Carter. "Potency of n-3 PUFA anti-inflammatory effects on human and rodent immune cell responses (111.16)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 111.16. http://dx.doi.org/10.4049/jimmunol.186.supp.111.16.
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Abstract Pharmaceutical parenteral emulsions consisting of n-6 poly-unsaturated fatty acids (PUFAs) alone (Intralipid®), n-6 PUFAs and n-9 mono-unsaturated fatty acids (MUFAs; e.g. Clinoleic®), n-3 PUFAs alone (Omegaven®), or a combination of n-3, n-6, n-9 and medium chain triglycerides (SMOF®) provide nutritional benefit to critical care patients, as well as influencing immune cell function. The efficacy of these compounds in modulating cell function varies depending on the formulation composition, route of administration, dose, and immune status of the individual. In general while n-9 MUFAs are neutral, n-6 PUFAs promote inflammatory responses. In contrast, n-3 PUFAs have immunosuppressive properties including blocking cell proliferation, cytokine production, and surface protein expression. However, there is limited data assessing the effects of n-3-containing pharmaceutical emulsions on immune cells across different species. In the current work, we determined the anti-inflammatory effects of n-3 PUFA-containing emulsions on an LPS-induced cytokine response in mouse, rat, and human mononuclear cells. We found that while n-3 PUFAs reduced the LPS-induced cytokine response in all species tested, these compounds were less potent in rodent cells compared to human cells. These findings provide insight into differences in the potency of n-3 PUFA anti-inflammatory effects across species and may be relevant for selecting the appropriate model system for assessing n-3 PUFAs efficacy in vivo.
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Liput, Kamila P., Adam Lepczyński, Magdalena Ogłuszka, Agata Nawrocka, Ewa Poławska, Agata Grzesiak, Brygida Ślaska, Chandra S. Pareek, Urszula Czarnik, and Mariusz Pierzchała. "Effects of Dietary n–3 and n–6 Polyunsaturated Fatty Acids in Inflammation and Cancerogenesis." International Journal of Molecular Sciences 22, no. 13 (June 28, 2021): 6965. http://dx.doi.org/10.3390/ijms22136965.
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The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.
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Simard, Mélissa, Pierre Julien, Julie Fradette, and Roxane Pouliot. "Modulation of the Lipid Profile of Reconstructed Skin Substitutes after Essential Fatty Acid Supplementation Affects Testosterone Permeability." Cells 8, no. 10 (September 25, 2019): 1142. http://dx.doi.org/10.3390/cells8101142.
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Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate whether PUFAs, alpha-linolenic acid (ALA, n-3 PUFA) and linoleic acid (LA, n-6 PUFA), could enhance the impermeability of a three-dimensional reconstructed human skin model, skin substitutes were produced according to the self-assembly method using culture media supplemented with either 10 μM ALA or 10 μM LA. The impact of PUFAs on skin permeability was studied by using a Franz cell diffusion system to assess the percutaneous absorption of testosterone and benzoic acid. Our findings showed that ALA supplementation induced a decrease in the absorption of testosterone, while LA supplementation did not significantly influence the penetration of testosterone and benzoic acid under present experimental conditions. Both ALA and LA were incorporated into phospholipids of the skin substitutes, resulting in an increase in n-3 total PUFAs or n-6 total PUFAs. Collectively, these results revealed the under-estimated impact of n-3 PUFA supplementation as well as the importance of the n-6 to n-3 ratio on the formation of the skin barrier of in vitro reconstructed human skin models.
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Acharya, Ranjitha, Shilpa S. Shetty, Flama Monteiro, Abhijith S. Shetty, and Suchetha Kumari N. "Delineating the antiproliferative activity of dietary polyunsaturated fatty acids on human breast cancer cells." Biomedicine 43, no. 6 (January 2, 2024): 1685–91. http://dx.doi.org/10.51248/.v43i6.3410.
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Introduction and Aim: The proliferation of breast cancer cells indicates that the malignancy is progressing to lethal forms. The development and progression of neoplastic cells are typically thought to be reliant on high cell proliferation and low apoptosis rates. Dietary polyunsaturated fatty acids (PUFA) aid in prevention of breast carcinoma. The current study objective is to evaluate the dietary PUFAs antiproliferative effect on human breast cancer cells. Material and Methods: The study utilized MDA MB-231 and MCF-7 cell lines which are specific to breast cancer. Cells were supplemented with free PUFAs after attaining 70% confluency in a cell viability assay. The cytotoxic effects of dietary PUFAs on these cells were assessed using MTT. Cell proliferation was analyzed using cell scratch assay and colony formation assay. Results: Dietary PUFAs reduced cell proliferation in a dose dependent way. Treatment with PUFA reduced cell growth, hindered colony formation and decreased migration in both the cell lines of breast carcinoma. Conclusion: The current research findings suggest that dietary PUFAs have an antiproliferative impact on human breast cancer cell lines and require further detailed study to identify the specific molecular mechanisms through which they exert anti-proliferative effect on breast cancer cells.
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Tilay, Ashwini, and Uday Annapure. "Novel Simplified and Rapid Method for Screening and Isolation of Polyunsaturated Fatty Acids Producing Marine Bacteria." Biotechnology Research International 2012 (August 15, 2012): 1–8. http://dx.doi.org/10.1155/2012/542721.
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Bacterial production of polyunsaturated fatty acids (PUFAs) is a potential biotechnological approach for production of valuable nutraceuticals. Reliable method for screening of number of strains within short period of time is great need. Here, we report a novel simplified method for screening and isolation of PUFA-producing bacteria by direct visualization using the H2O2-plate assay. The oxidative stability of PUFAs in growing bacteria towards added H2O2 is a distinguishing characteristic between the PUFAs producers (no zone of inhibition) and non-PUFAs producers (zone of inhibition) by direct visualization. The confirmation of assay results was performed by injecting fatty acid methyl esters (FAMEs) produced by selected marine bacteria to Gas Chromatography-Mass Spectrometry (GCMS). To date, this assay is the most effective, inexpensive, and specific method for bacteria producing PUFAs and shows drastically reduction in the number of samples thus saves the time, effort, and cost of screening and isolating strains of bacterial PUFAs producers.
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Di Miceli, Mathieu, Maud Martinat, Moïra Rossitto, Agnès Aubert, Shoug Alashmali, Clémentine Bosch-Bouju, Xavier Fioramonti, Corinne Joffre, Richard P. Bazinet, and Sophie Layé. "Dietary Long-Chain n-3 Polyunsaturated Fatty Acid Supplementation Alters Electrophysiological Properties in the Nucleus Accumbens and Emotional Behavior in Naïve and Chronically Stressed Mice." International Journal of Molecular Sciences 23, no. 12 (June 14, 2022): 6650. http://dx.doi.org/10.3390/ijms23126650.
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Long-chain (LC) n-3 polyunsaturated fatty acids (PUFAs) have drawn attention in the field of neuropsychiatric disorders, in particular depression. However, whether dietary supplementation with LC n-3 PUFA protects from the development of mood disorders is still a matter of debate. In the present study, we studied the effect of a two-month exposure to isocaloric diets containing n-3 PUFAs in the form of relatively short-chain (SC) (6% of rapeseed oil, enriched in α-linolenic acid (ALA)) or LC (6% of tuna oil, enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) PUFAs on behavior and synaptic plasticity of mice submitted or not to a chronic social defeat stress (CSDS), previously reported to alter emotional and social behavior, as well as synaptic plasticity in the nucleus accumbens (NAc). First, fatty acid content and lipid metabolism gene expression were measured in the NAc of mice fed a SC (control) or LC n-3 (supplemented) PUFA diet. Our results indicate that LC n-3 supplementation significantly increased some n-3 PUFAs, while decreasing some n-6 PUFAs. Then, in another cohort, control and n-3 PUFA-supplemented mice were subjected to CSDS, and social and emotional behaviors were assessed, together with long-term depression plasticity in accumbal medium spiny neurons. Overall, mice fed with n-3 PUFA supplementation displayed an emotional behavior profile and electrophysiological properties of medium spiny neurons which was distinct from the ones displayed by mice fed with the control diet, and this, independently of CSDS. Using the social interaction index to discriminate resilient and susceptible mice in the CSDS groups, n-3 supplementation promoted resiliency. Altogether, our results pinpoint that exposure to a diet rich in LC n-3 PUFA, as compared to a diet rich in SC n-3 PUFA, influences the NAc fatty acid profile. In addition, electrophysiological properties and emotional behavior were altered in LC n-3 PUFA mice, independently of CSDS. Our results bring new insights about the effect of LC n-3 PUFA on emotional behavior and synaptic plasticity.
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Walker, Rachel E., Valentina Parkhomenko, Yun Ying, Natalie Urrutia, and Kevin J. Harvatine. "Dietary SFAs and ω-6 Fatty Acids Alter Incorporation of ω-3 Fatty Acids into Milk Fat of Lactating CD-1 Mice and Tissues of Offspring." Journal of Nutrition 151, no. 7 (May 19, 2021): 1834–43. http://dx.doi.org/10.1093/jn/nxab094.
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ABSTRACT Background Methods to increase the amount of omega-3 (n–3) PUFAs in milk are desirable for neonatal health. The n–3 PUFA, α-linolenic acid (18:3n–3), can be elongated to EPA (20:5n–3) and DHA (22:6n–3). n–6 PUFAs suppress tissue n–3 PUFA incorporation, but the effect of SFAs is not clear. Objectives In this study, we compared the effects of SFAs and n–6 PUFAs on n–3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring. Methods Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect. Results Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n–3 PUFAs (SAT: −23%; HLA: −31%) compared with LFD, and HLA increased milk n–6 FAs by 347% compared with SAT. SAT pups had n–3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n–3 PUFAs than SAT pups in multiple tissues (liver, −32%; kidney, −29%; heart, −28%; muscle, −18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, −42%; Elov6, −64%; fatty acid desaturase (Fads)1, −33%; Fads2, −44%]. Conclusions HLA decreased n–3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n–6 PUFAs suppress n–3 PUFA incorporation in neonates.
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Mihalj, Martina, Ana Stupin, Nikolina Kolobarić, Ivana Tartaro Bujak, Anita Matić, Zlata Kralik, Ivana Jukić, Marko Stupin, and Ines Drenjančević. "Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study." Nutrients 12, no. 10 (October 13, 2020): 3122. http://dx.doi.org/10.3390/nu12103122.
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This placebo-controlled, double-blind, randomized, interventional study investigated the effects of low/intermediate doses of n-3 polyunsaturated fatty acids (PUFAs) on the endothelial function, markers of leukocyte activation, and oxidative status following dietary intake of n-3 PUFA-enriched hen eggs in young healthy individuals. Twenty young healthy adults of both sexes who consumed n-3 PUFA-enriched hen eggs (two eggs per day, for three weeks, total of approximately 407 mg/day n-3 PUFAs) or regular eggs (two eggs per day for three weeks, total of approximately 75 mg/day n-3 PUFAs) participated in this study. Skin microvascular endothelium-independent and endothelium-dependent vasodilation were assessed by laser Doppler flowmetry. Serum lipid profile and content of free fatty acids, markers of leukocyte activation, biochemical parameters of oxidative stress, as well as antioxidative enzymes serum activity were measured before and after respective dietary protocol. The results of this study revealed significant differences in the markers of leukocyte activation (such as CD11a/LFA-1) and antioxidative defense, which are related to increased intake of n-3 PUFAs, providing the evidence that consumption of nutritionally enriched hen eggs may affect physiological processes related to oxidative balance. The absence of significant changes in microvascular reactivity following supplementation with a low-intermediate dose of n-3 PUFAs, unlike in our previous studies where functional eggs contained ~1 g of n-3 PUFA, suggests the existence of a dose-dependent effect.
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Czumaj, Aleksandra, and Tomasz Śledziński. "Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease." Nutrients 12, no. 2 (January 29, 2020): 356. http://dx.doi.org/10.3390/nu12020356.
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Polyunsaturated fatty acids (PUFAs) are considered one of the most important components of cells that influence normal development and function of many organisms, both eukaryotes and prokaryotes. Unsaturated fatty acid desaturases play a crucial role in the synthesis of PUFAs, inserting additional unsaturated bonds into the acyl chain. The level of expression and activity of different types of desaturases determines profiles of PUFAs. It is well recognized that qualitative and quantitative changes in the PUFA profile, resulting from alterations in the expression and activity of fatty acid desaturases, are associated with many pathological conditions. Understanding of underlying mechanisms of fatty acid desaturase activity and their functional modification will facilitate the development of novel therapeutic strategies in diseases associated with qualitative and quantitative disorders of PUFA.
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Shrestha, Pushkar, Xue-Rong Zhou, Sapna Vibhakaran Pillai, James Petrie, Robert de Feyter, and Surinder Singh. "Comparison of the Substrate Preferences of ω3 Fatty Acid Desaturases for Long Chain Polyunsaturated Fatty Acids." International Journal of Molecular Sciences 20, no. 12 (June 22, 2019): 3058. http://dx.doi.org/10.3390/ijms20123058.
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Omega-3 long chain polyunsaturated fatty acids (ω3 LC-PUFAs) such as eicosapentaenoic acid (EPA; 20:5ω3) and docosahexaenoic acid (DHA; 22:6ω3) are important fatty acids for human health. These ω3 LC-PUFAs are produced from their ω3 precursors by a set of desaturases and elongases involved in the biosynthesis pathway and are also converted from ω6 LC-PUFA by omega-3 desaturases (ω3Ds). Here, we have investigated eight ω3-desaturases obtained from a cyanobacterium, plants, fungi and a lower animal species for their activities and compared their specificities for various C18, C20 and C22 ω6 PUFA substrates by transiently expressing them in Nicotiana benthamiana leaves. Our results showed hitherto unreported activity of many of the ω3Ds on ω6 LC-PUFA substrates leading to their conversion to ω3 LC-PUFAs. This discovery could be important in the engineering of EPA and DHA in heterologous hosts.
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Ostermann, Annika I., Annette L. West, Kirsten Schoenfeld, Lucy M. Browning, Celia G. Walker, Susan A. Jebb, Philip C. Calder, and Nils Helge Schebb. "Plasma oxylipins respond in a linear dose-response manner with increased intake of EPA and DHA: results from a randomized controlled trial in healthy humans." American Journal of Clinical Nutrition 109, no. 5 (April 21, 2019): 1251–63. http://dx.doi.org/10.1093/ajcn/nqz016.
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ABSTRACT Background The health effects of long-chain omega-3 polyunsaturated fatty acids (n–3 PUFAs) are partly mediated by their oxidized metabolites, i.e., eicosanoids and other oxylipins. Some intervention studies have demonstrated that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase systemic concentrations of n–3 PUFA–derived oxylipins and moderately decrease arachidonic acid–derived oxylipins. There is no information on the dose-response of oxylipin concentrations after n–3 PUFA intake. Objective The aim of this study was to quantify oxylipins in human plasma samples from an intervention study in which participants were randomly assigned to different daily intakes of EPA and DHA for 12 mo. Methods Healthy adult men and women with low habitual fish consumption (n = 121) were randomly assigned to receive capsules providing doses of n–3 PUFAs reflecting 3 patterns of consumption of oily fish [1, 2, or 4 portions/wk with 3.27 g EPA + DHA (1:1.2, wt:wt) per portion] or placebo. Oxylipins were quantified in plasma after 3 and 12 mo. Relative and absolute changes of individual oxylipins were calculated and concentrations were correlated with the dose and the content of EPA and DHA in blood lipid pools. Results Seventy-three oxylipins, mostly hydroxy-, dihydroxy-, and epoxy-PUFAs, were quantified in the plasma samples. After 3 and 12 mo a linear increase with dose was observed for all EPA- and DHA-derived oxylipins. Cytochrome-P450-derived anti-inflammatory and cardioprotective epoxy-PUFAs increased linearly with n–3 PUFA dose and showed low interindividual variance (r2 > 0.95). Similarly, 5, 12-, and 15-lipoxygenase–derived hydroxy-PUFAs as well as those formed autoxidatively increased linearly. These include the precursors of so-called specialized pro-resolving lipid mediators (SPMs), e.g., 17-hydroxy-DHA and 18-hydroxy-EPA. Conclusions Plasma concentrations of biologically active oxylipins derived from n–3 PUFAs, including epoxy-PUFAs and SPM-precursors, increase linearly with elevated intake of EPA and DHA. Interindividual differences in resulting plasma concentrations are low. This trial was registered at controlled-trials.com as ISRCTN48398526.
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Zhang, Yan, Xiao-Qing Sun, Yu-Qing Ye, Qi Wang, Qing-Song Li, Ran Zhao, Hong-Wei Wang, and Jiong-Tang Li. "Association between the Polymorphisms of fads2a and fads2b and Poly-Unsaturated Fatty Acids in Common Carp (Cyprinus carpio)." Animals 11, no. 6 (June 15, 2021): 1780. http://dx.doi.org/10.3390/ani11061780.
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Fatty acid desaturase 2 (fads2) is one of the rate-limiting enzymes in PUFAs biosynthesis. Compared with the diploid fish encoding one fads2, the allo-tetraploid common carp, one most important food fish, encodes two fads2 genes (fads2a and fads2b). The associations between the contents of different PUFAs and the polymorphisms of fads2a and fads2b have not been studied. The contents of 12 PUFAs in common carp individuals were measured, and the polymorphisms in the coding sequences of fads2a and fads2b were screened. We identified five coding single nucleotide polymorphisms (cSNPs) in fads2a and eleven cSNPs in fads2b. Using the mixed linear model and analysis of variance, a synonymous fads2a cSNP was significantly associated with the content of C20:3n-6. One non-synonymous fads2b cSNP (fads2b.751) and one synonymous fads2b cSNP (fads2b.1197) were associated with the contents of seven PUFAs and the contents of six PUFAs, respectively. The heterozygous genotypes in both loci were associated with higher contents than the homozygous genotypes. The fads2b.751 genotype explained more phenotype variation than the fads2b.1197 genotype. These two SNPs were distributed in one haplotype block and associated with the contents of five common PUFAs. These results suggested that fads2b might be the major gene responding to common carp PUFA contents and that fads.751 might be the main effect SNP. These cSNPs would be potential markers for future selection to improve the PUFA contents in common carp.
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Gorusupudi, Aruna, Rameshu Rallabandi, Binxing Li, Ranganathan Arunkumar, J. David Blount, Gregory T. Rognon, Fu-Yen Chang, et al. "Retinal bioavailability and functional effects of a synthetic very-long-chain polyunsaturated fatty acid in mice." Proceedings of the National Academy of Sciences 118, no. 6 (February 1, 2021): e2017739118. http://dx.doi.org/10.1073/pnas.2017739118.
Full textAbstract:
Rare, nondietary very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are uniquely found in the retina and a few other vertebrate tissues. These special fatty acids play a clinically significant role in retinal degeneration and development, but their physiological and interventional research has been hampered because pure VLC-PUFAs are scarce. We hypothesize that if Stargardt-3 or age-related macular degeneration patients were to consume an adequate amount of VLC-PUFAs that could be directly used in the retina, it may be possible to bypass the steps of lipid elongation mediated by the retina’s ELOVL4 enzyme and to delay or prevent degeneration. We report the synthesis of a VLC-PUFA (32:6 n-3) in sufficient quantity to study its bioavailability and functional benefits in the mouse retina. We acutely and chronically gavage fed wild-type mice and Elovl4 rod–cone conditional knockout mice this synthetic VLC-PUFA to understand its bioavailability and its role in visual function. VLC-PUFA-fed wild-type and Elovl4 conditional knockout mice show a significant increase in retinal VLC-PUFA levels in comparison to controls. The VLC-PUFA-fed mice also had improvement in the animals’ visual acuity and electroretinography measurements. Further studies with synthetic VLC-PUFAs will continue to expand our understanding of the physiological roles of these unique retinal lipids, particularly with respect to their potential utility for the treatment and prevention of retinal degenerative diseases.
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Aarsetoey, Hildegunn, Heidi Grundt, Ottar Nygaard, and Dennis W. T. Nilsen. "The Role of Long-Chained Marine N-3 Polyunsaturated Fatty Acids in Cardiovascular Disease." Cardiology Research and Practice 2012 (2012): 1–15. http://dx.doi.org/10.1155/2012/303456.
Full textAbstract:
This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.
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Fu, Yawei, Yadong Wang, Hu Gao, DongHua Li, RuiRui Jiang, Lingrui Ge, Chao Tong, and Kang Xu. "Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity." Mediators of Inflammation 2021 (January 2, 2021): 1–11. http://dx.doi.org/10.1155/2021/8879227.
Full textAbstract:
Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs–microbiome–immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.
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Hill, V. L., and G. L. Florant. "Patterns of fatty acid composition in free-ranging yellow-bellied marmots (Marmota flaviventris) and their diet." Canadian Journal of Zoology 77, no. 9 (November 15, 1999): 1494–503. http://dx.doi.org/10.1139/z99-132.
Full textAbstract:
In the laboratory, dietary polyunsaturated fatty acids (PUFAs) are conserved in the tissues of hibernators and are important for normal hibernation. Prior to this study, it was unknown if PUFAs are similarly conserved in the tissues of free-ranging hibernators or how the concentration of these PUFAs change in the natural diet over the summer. Therefore, we analyzed the fatty acid composition of the white adipose tissue (WAT) and plasma of free-ranging marmots (Marmota flaviventris) and of the plants in the marmots' diet, throughout the year. Marmots store PUFAs in WAT prior to hibernation but, over the winter, the percentage of the n-6 PUFA linoleic acid (18:2) increased in WAT, while the percentage of the n-3 PUFA α-linolenic acid (α-18:3) decreased in WAT. In the plasma, the concentration of nonesterified saturated and monounsaturated fatty acids was greater than that of nonesterified PUFAs, particularly in the spring. In the natural diet, the concentration of fatty acids varied significantly between plant species and between parts of the same plant. These data for free-ranging marmots corroborate previous results from studies on hibernators in the laboratory and, in addition, provide new information about the role of α-18:3 in hibernation.
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Gao, Yan, Xiaowen Hu, Dandan Wang, Jie Jiang, Minghui Li, Ying Qing, Xuhan Yang, Juan Zhang, Yue Zhang, and Chunling Wan. "Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis." Nutrients 15, no. 5 (February 27, 2023): 1195. http://dx.doi.org/10.3390/nu15051195.
Full textAbstract:
Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (rAA = −0.577, p < 0.01; rω-6 LCPUFA = −0.626, p < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (ORAA = 0.986, ORGLA = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia.
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Malinowska, Malwina Anna, Oskar Wojciech Wiśniewski, and Magdalena Warchoł. "Single nucleotide polymorphisms in desaturases genes – effect on docosahexaenoic acid levels in maternal and fetal tissues and early development of the child." Journal of Medical Science 86, no. 2 (July 5, 2017): 177. http://dx.doi.org/10.20883/jms.2016.237.
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Polyunsaturated fatty acids (PUFAs) beneficially affect an optimal fetal growth and development right after birth. This effect is particularly significant for the growth and maturation of brain. Therefore, an appropriate maternal regimens for PUFAs supplementation, during pregnancy and lactation, may influence birth outcome and infant health. Recently, it has been shown that genetic profile is an another factor determining long‑chain polyunsaturated fatty acids (LC‑PUFA) composition in human tissues. Single Nucleotide Polymorphisms (SNPs) in the fatty desaturase 1 and 2 (FADS1 and FADS2) modify endogenous synthesis of PUFAs indicating that PUFAs blood concentration may depend on genetic background. What is more, a number of studies indicate that maternal FADS gene variants by their influence on LC‑PUFAs synthesis are associated with child’s health right after birth as well as within first years of life. Determining individual dietary recommendations for clinical practice can be beneficial for both mother and the child.
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Freitas, Raquel, and Maria M. Campos. "Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications." Nutrients 11, no. 5 (April 26, 2019): 945. http://dx.doi.org/10.3390/nu11050945.
Full textAbstract:
Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.
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Suzuki, Nobuaki, Kaori Sawada, Ippei Takahashi, Motoko Matsuda, Shinji Fukui, Hidemasa Tokuyasu, Hiroyasu Shimizu, Junichi Yokoyama, Arata Akaike, and Shigeyuki Nakaji. "Association between Polyunsaturated Fatty Acid and Reactive Oxygen Species Production of Neutrophils in the General Population." Nutrients 12, no. 11 (October 22, 2020): 3222. http://dx.doi.org/10.3390/nu12113222.
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Little is known about the relationship between polyunsaturated fatty acids (PUFAs) and reactive oxygen species (ROS) in the general population. Therefore this study aimed to describe the association of PUFAs with ROS according to age and sex in the general population and to determine whether PUFA levels are indicators of ROS. This cross-sectional study included 895 participants recruited from a 2015 community health project. Participants were divided into 6 groups based on sex and age (less than 45 years old (young), aged 45–64 years (middle-aged), and 65 years or older (old)) as follows: male, young (n = 136); middle-aged (n = 133); old (n = 82); female, young (n = 159); middle-aged (n = 228); and old (n = 157). The PUFAs measured were arachidonic acid (AA), dihomo gamma linolenic acid (DGLA), AA/DGLA ratio, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ROS considered in the analysis were basal ROS and stimulated ROS levels. Multiple linear analyses showed: (1) significant correlations between PUFA levels, especially DGLA and AA/DGLA ratio, and neutrophil function in the young and middle-aged groups; (2) no significant correlations in old age groups for either sex. Because PUFAs have associated with the ROS production, recommendation for controlled PUFA intake from a young age should be considered.
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Maucher, Daniel, Birte Schmidt, Kevin Kuhlmann, and Julia Schumann. "Polyunsaturated Fatty Acids of Both the Omega-3 and the Omega-6 Family Abrogate the Cytokine-Induced Upregulation of miR-29a-3p by Endothelial Cells." Molecules 25, no. 19 (September 29, 2020): 4466. http://dx.doi.org/10.3390/molecules25194466.
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Cellular processes fundamentally depend on protein expression control. At this, protein expression is regulated on the transcriptional and the post-transcriptional level. PUFAs are already known to affect gene transcription. The present study was conducted to answer the question whether PUFAs are also able to impact on the miRNA-mediated post-transcriptional fine-tuning of mRNA copy numbers. To this end, cellular miRNA profiles were screened by means of next-generation sequencing and NanoString analysis to compare PUFA-enriched to unsupplemented endothelial cells exposed to an inflammatory milieu. Validation took place by droplet digital PCR, allowing for an absolute quantification of RNA copy numbers. The analyses revealed that the stimulation-induced upregulation of miR-29a-3p is blocked by PUFA enrichment of endothelial cells. What is more, mRNA copy numbers of miR-29a-3p targets, namely the coagulation factors PAI-1, TF, and vWF, as well as the proinflammatory cytokines IL-1β, IL-6, and IL-8, were reduced in PUFA-enriched endothelial cells compared to unsupplemented cells, counteracting the stimulatory effect of an inflammatory environment. These data hint toward a new mechanism of action by which PUFAs modulate the functionality of endothelial cells. Apparently, the inflammation-modulating properties of PUFAs are also mediated at the post-transcriptional level.
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D`Archivio, Massimo, Beatrice Scazzocchio, Rosaria Vari, Carmela Santangelo, Claudio Giovannini, and Roberta Masella. "Recent Evidence on the Role of Dietary PUFAs in Cancer Development and Prevention." Current Medicinal Chemistry 25, no. 16 (May 9, 2018): 1818–36. http://dx.doi.org/10.2174/0929867325666171204160231.
Full textAbstract:
Background: Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. Methods: We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Results: Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. Conclusion: N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.
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Chénais, Benoît, and Vincent Blanckaert. "The Janus Face of Lipids in Human Breast Cancer: How Polyunsaturated Fatty Acids Affect Tumor Cell Hallmarks." International Journal of Breast Cancer 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/712536.
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For several years, lipids and especially and polyunsaturated fatty acids (PUFAs) receive much attention in human health. Epidemiological studies tend to correlate a PUFA-rich diet with a reduced incidence of cancer, including breast cancer. However, the molecular and cellular mechanisms supporting the effect of PUFAs in breast cancer cells remain relatively unknown. Here, we review some recent progress in understanding the impact that PUFA may have on breast cancer cell proliferation, apoptosis, migration, and invasion. While most of the results obtained with docosahexaenoic acid and/or eicosapentaenoic acid show a decrease of tumor cell proliferation and/or aggressivity, there is some evidence that other lipids, which accumulate in breast cancer tissues, such as arachidonic acid may have opposite effects. Finally, lipids and especially PUFAs appear as potential adjuvants to conventional cancer therapy.
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Aleksandra Lyudinina and Evgeny Boyko. "Imbalance of n6/n3 fatty acids in the training period and after competition in cross-country Skiers." International Journal of Physical Education, Fitness and Sports 8, no. 3 (August 15, 2019): 1–6. http://dx.doi.org/10.26524/ijpefs1931.
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The aim of the study was to investigate the level of essential polyunsaturated fatty acids (PUFAs) in athletes into the training period and after endurance race (n=15 high-trained male cross-country skiers, real members of national skiing team). The PUFAs in plasma was determined by the gas-liquid chromatography method. Results demonstrate a deficiency of plasma level of the n-3 PUFA of the almost all skiers during the training period. Competition activity modified the essential PUFA profile in blood across more twice increase of the n-3 docosahexaenoic acids (DHA) (p=0.112) and n-3 alpha-linolenic (ALA) (p=0.048) levels and decrease n-6 PUFA relative to baselines, which expressed in a decrease in n6/n3 ratio (p=0.017). Relationships between n3/n-6 ratio and base heart rate, diastolic pressure and Maximal oxygen uptake, show on the significant role essential PUFAs in regulation of the cardiovascular system in cross-country skiers.
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Aleksandra Lyudinina and Evgeny Boyko. "Imbalance of n6/n3 fatty acids in the training period and after competition in cross-country Skiers." International Journal of Physical Education, Fitness and Sports 8, no. 3 (September 30, 2019): 1–6. http://dx.doi.org/10.26524/jpefs1931.
Full textAbstract:
The aim of the study was to investigate the level of essential polyunsaturated fatty acids (PUFAs) in athletes into the training period and after endurance race (n=15 high-trained male cross-country skiers, real members of national skiing team). The PUFAs in plasma was determined by the gas-liquid chromatography method. Results demonstrate a deficiency of plasma level of the n-3 PUFA of the almost all skiers during the training period. Competition activity modified the essential PUFA profile in blood across more twice increase of the n-3 docosahexaenoic acids (DHA) (p=0.112) and n-3 alpha-linolenic (ALA) (p=0.048) levels and decrease n-6 PUFA relative to baselines, which expressed in a decrease in n6/n3 ratio (p=0.017). Relationships between n-3/n-6 ratio and base heart rate, diastolic pressure and Maximal oxygen uptake, show on the significant role essential PUFAs in regulation of the cardiovascular system in cross-country skiers.
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Crippa, Alessandro, Carlo Agostoni, Maddalena Mauri, Massimo Molteni, and Maria Nobile. "Polyunsaturated Fatty Acids Are Associated With Behavior But Not With Cognition in Children With and Without ADHD: An Italian study." Journal of Attention Disorders 22, no. 10 (February 9, 2016): 971–83. http://dx.doi.org/10.1177/1087054716629215.
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Objective: This study aimed to investigate the relationship between polyunsaturated fatty acids (PUFAs) status, cognitive, and behavioral traits of ADHD in school-aged children. Method: Seventy-three children with and without ADHD were assessed with cognitive tasks and behavioral rating scales including quality of life and global functioning at baseline of an intervention trial (clinicaltrials.gov NCT01796262). Correlation analyses were performed between the cognitive tasks/behavioral ratings and blood PUFA levels. Results: Children with ADHD had lower levels of DHA, omega-3 index, and total PUFA. PUFAs were positively associated with behavior but not consistently related to cognitive domains. Conclusion: The present study confirms that children with ADHD display abnormal fatty acid profiles within an Italian setting. Furthermore, PUFAs were associated with behavior but not with cognition. Accordingly, for the first time, lower blood levels of PUFA were associated not only with symptoms of ADHD but also with a poorer quality of life.