Dietary Polyunsaturated Fatty Acid Supplementation Research Articles

Modification in mitochondrial function is associated with the FADS1 variant and its interaction with alpha-linolenic acid-enriched diet—An exploratory study

Fatty acid desaturase (FADS1) variant-rs174550 strongly regulates polyunsaturated fatty acid (PUFA) biosynthesis. Additionally, the FADS1 is related to mitochondrial function. Thus, we investigated whether changes in mitochondrial function are associated with the genetic variation in FADS1 (rs174550) in human adipocytes isolated from individuals consuming diets enriched with either dietary alpha-linolenic (ALA) or linoleic acid (LA). Two cohorts of men homozygous for the genotype of FADS1 (rs174550) were studied: FADSDIET2 dietary intervention study with ALA- and LA-enriched diets and Kuopio Obesity Surgery study (KOBS), respectively. We could demonstrate that differentiated human adipose-derived stromal cells from subjects with the TT genotype had higher mitochondrial metabolism compared with subjects with the CC genotype of FADS1-rs174550 in the FADSDIET2. Responses to PUFA-enriched diets differed between the genotypes of FADS1-rs174550, showing that ALA, but not LA, -enriched diet stimulated mitochondrial metabolism more in subjects with the CC genotype when compared with subjects with the TT genotype. ALA, but not LA, proportion in plasma phospholipid fraction correlated positively with adipose tissue mitochondrial-DNA amount in subjects with the CC genotype of FADS1-rs174550 in the KOBS. These findings demonstrate that the FADS1-rs174550 is associated with modification in mitochondrial function in human adipocytes. Additionally, subjects with the CC genotype, when compared with the TT genotype, benefit more from the ALA-enriched diet, leading to enhanced energy metabolism in human adipocytes. Altogether, the FADS1-rs174550 could be a genetic marker to identify subjects who are most suitable to receive dietary PUFA supplementation, establishing also a personalized therapeutic strategy to improve mitochondrial function in metabolic diseases.

Effects of omega-3, omega-6, and total dietary polyunsaturated fatty acid supplementation in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Background: Uncertainty exists about the link between omega-3 fatty acid, omega-6 fatty acid, and total polyunsaturated fatty acid (PUFA) intake and mortality in atherosclerotic cardiovascular disease (ASCVD) patients, and no meta-analyses summarize the relationship between these various types of PUFAs and ASCVD. Methods: Web of Science, PubMed, EBSCO and Cochrane Library up to November 30, 2022 were searched for prospective randomized controlled studies investigating the relationships among omega-3, omega-6, and PUFA intake and mortality and cardiovascular events in ASCVD patients. This study has been registered at PROSPERO (No. CRD42023407566). Results: This meta-analysis included 21 publications from 17 studies involving 40 861 participants published between 1965 and 2022. In ASCVD patients, omega-3 may lower all-cause mortality (RR: 0.90, 95% CI [0.83, 0.98], I2 = 8%), CVD mortality (RR: 0.82, 95% CI [0.73, 0.91], I2 = 34%) and CVD events (RR: 0.90, 95% CI [0.86, 0.93], I2 = 79%). Subgroup analyses showed that EPA or EPA ethyl ester supplementation reduced CVD events, while the mixture of EPA and DHA had no significant impact. Long-chain omega-3 consumption of 1.0-4.0 g per d reduced death risk by 3.5% for each 1 g per d increase. Omega-6 and PUFA had no significant effect on mortality or CVD events, with low-quality evidence and significant heterogeneity. Conclusions: omega-3 intake is associated with a reduced risk of all-cause mortality, CVD mortality, and CVD events in ASCVD patients, while omega-6 or total PUFA intake showed no significant association. Increasing the omega-3 intake by 1 g per d resulted in a 3.5% decrease in the risk of death. These findings support the recommendation of supplements with omega-3 fatty acids for the secondary prevention of ASCVD.

Inhibition of ACLY overcomes cancer immunotherapy resistance via polyunsaturated fatty acids peroxidation and cGAS-STING activation.

Adenosine 5'-triphosphate citrate lyase (ACLY) is a cytosolic enzyme that converts citrate into acetyl-coenzyme A for fatty acid and cholesterol biosynthesis. ACLY is up-regulated or activated in many cancers, and targeting ACLY by inhibitors holds promise as potential cancer therapy. However, the role of ACLY in cancer immunity regulation remains poorly understood. Here, we show that ACLY inhibition up-regulates PD-L1 immune checkpoint expression in cancer cells and induces T cell dysfunction to drive immunosuppression and compromise its antitumor effect in immunocompetent mice. Mechanistically, ACLY inhibition causes polyunsaturated fatty acid (PUFA) peroxidation and mitochondrial damage, which triggers mitochondrial DNA leakage to activate the cGAS-STING innate immune pathway. Pharmacological and genetic inhibition of ACLY overcomes cancer resistance to anti-PD-L1 therapy in a cGAS-dependent manner. Furthermore, dietary PUFA supplementation mirrors the enhanced efficacy of PD-L1 blockade by ACLY inhibition. These findings reveal an immunomodulatory role of ACLY and provide combinatorial strategies to overcome immunotherapy resistance in tumors.

Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults

OBJECTIVEDietary fat intake was considered as a modifiable factor influencing cognitive performance. The objective was to 1) examine the associations between different types of dietary fat intakes and cognitive outcomes among elder adults (≥60 years old); 2) assess whether peripheral oxidative stress and antioxidant biomarkers are potential mediators of dietary fat intake and cognitive impairment relationship. METHODSUsing data from National Health and Nutrition Examination Survey 2011-2014, total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, ω-3 and ω-6 fatty acids were used to evaluate dietary fat intakes. Cognitive outcomes were assessed by word learning and recall modules from the consortium to establish a registry for Alzheimer's Disease (CERAD), animal fluency test, and digit symbol substitution test (DSST). Antioxidant biomarkers were assessed by gamma glutamyl transpeptidase (GGT), bilirubin, uric acid, and vitamin D levels. Linear regression models and causal mediation analysis were applied to quantify the associations. RESULTSA total of 2,253 elder adults were included in the data analyses. Dietary intake of PUFA and ω-6 fatty acid were positively associated with DSST [β (95% CI): 0.06 (0.01,0.10), t statistic = 2.39, df= 2238, p = 0.02; β (95% CI): 0.06 (0.01,0.11), t statistic = 2.54, df= 2238, p = 0.01, respectively]. GGT was negatively associated with DSST [β (95% CI): -0.04 (-0.07, -0.01), t statistic = -2.73, df= 2239, p = 0.01], whereas uric acid was positively associated with CERAD total score [β (95% CI): 0.04 (0.00,0.08), t statistic = 2.03, df= 2233, p = 0.04]. The association between dietary intake of PUFA/ω -3/ω -6 and DSST performance was partially mediated by GGT level. CONCLUSIONOur findings support that PUFAs in dietary sources were associated with lower risks for cognitive impairment partially via lowering oxidative stress. Dietary PUFA supplementation may potentially reduce risk of cognitive impairment via antioxidative mechanism.

Dietary polyunsaturated fatty acid supply improves Daphnia performance at fluctuating temperatures, simulating diel vertical migration

Abstract Diel vertical migration (DVM) is a common predator avoidance strategy of zooplankton. Migration to deeper water layers during the day to escape visually hunting predators is most likely to require physiological adaptations to periodically changing temperatures. Polyunsaturated fatty acids (PUFA) play crucial roles in membrane temperature acclimation. Exposure to cold temperatures typically results in an increase in the relative abundance of PUFA in cell membranes and PUFA requirements of Daphnia increase with decreasing temperatures. To assess the role of dietary PUFA in coping with temperature fluctuations experienced during DVM, we reared Daphnia magna at either constantly warm or fluctuating temperatures, simulating DVM both with and without dietary PUFA supplementation. We show that the well‐known positive effect of dietary eicosapentaenoic acid supplementation on offspring production and population growth rates of D. magna is more pronounced at alternating temperatures than at constantly warm temperatures. Exposure to alternating temperatures caused modification in body PUFA concentrations and, consequently, increased lipid peroxidation. However, detrimental effects of lipid peroxidation were not evident. Our data demonstrate that the capacity to cope with the distinct temperature fluctuations experienced during DVM increases with dietary eicosapentaenoic acid supplementation, suggesting that an adequate dietary PUFA supply is crucial especially for migrating Daphnia populations. A dietary deficiency in long‐chain PUFA may thus severely constrain predator evasion, potentially resulting in increased mortality and cascading effects on lower trophic levels.

The Eye, Oxidative Damage and Polyunsaturated Fatty Acids.

Polyunsaturated fatty acids (PUFA) are known to have numerous beneficial effects, owing to their anti-inflammatory and antioxidant properties. From a metabolic standpoint, the mitochondria play a fundamental role in cellular homeostasis, and oxidative stress can affect their functioning. Indeed, the mitochondria are the main source of ROS, and an imbalance between ROS and antioxidant defenses leads to oxidative stress. In addition, aging, the decline of cellular functions, and continual exposure to light underlie many diseases, particularly those of the eye. Long-term exposure to insults, such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins, contribute to oxidative damage in ocular tissues and expose the aging eye to considerable risk of pathological consequences of oxidative stress. Ample antioxidant defenses responsible for scavenging free radicals are essential for redox homeostasis in the eye, indeed, eye tissues, starting from the tear film, which normally are exposed to high oxygen levels, have strong antioxidant defenses that are efficient for protecting against ROS-related injuries. On the contrary, instead, the trabecular meshwork is not directly exposed to light and its endothelial cells are poorly equipped with antioxidant defenses. All this makes the eye a target organ of oxidative damage. This review focuses on the role of the polyunsaturated fatty acids in the human eye, particularly in such pathologies as dry eye, glaucoma, and macular degeneration, in which dietary PUFA supplementation can be a valid therapeutic aid.

Dietary polyunsaturated fatty acid supplementation of young post-pubertal dairy bulls alters the fatty acid composition of seminal plasma and spermatozoa but has no effect on semen volume or sperm quality

The aim of this study was to examine the effects of dietary supplementation with rumen protected n-6 or n-3 polyunsaturated fatty acids (PUFA) on the quantity and quality of semen from young post-pubertal dairy bulls. Pubertal Holstein-Friesian (n = 43) and Jersey (n = 7) bulls with a mean ± s.e.m. age and bodyweight of 420.1 ± 5.86 days and 382 ± 8.94 kg, respectively, were blocked on breed, weight, age and semen quality (based on the outcomes of two pre-trial ejaculates) and randomly assigned to one of three treatments: (i) a non-supplemented control (CTL, n = 15), (ii) rumen-protected safflower (SO, n = 15), (iii) rumen-protected n-3 PUFA-enriched fish oil (FO, n = 20). Bulls were fed their respective diets, ad libitum for 12 weeks; individual intakes were recorded using an electronic feeding system for the initial 6 weeks of the feeding period. Semen was collected via electro-ejaculation at weeks −2, −1, 0, 7, 10, 11 and 12 relative to the beginning of the trial period (week 0). On collection, semen volume, sperm concentration and progressive linear motility (PLM) were assessed. On weeks −2, −1, 0, 10, 11, 12, semen was packaged into 0.25 mL straws and frozen using a programmable freezer. On weeks −1, 7 and 11; a sub-sample of semen was separated into sperm and seminal plasma, by centrifugation and stored at – 20 °C until analysis of lipid composition. Semen from 10 bulls per treatment were used for post-thaw analysis at weeks 10, 11 and 12 (3 straws per ejaculate). Sperm motility was analysed by computer assisted semen analysis (CASA). In addition, membrane fluidity, acrosome reaction and oxidative stress were assessed using flow cytometry. Sperm from bulls fed SO had a 1.2 fold higher total n-6 PUFA content at week 11 compared to week −1 (P < 0.01) while bulls fed FO had a 1.3 fold higher total n-3 PUFA content, in sperm by week 11 (P < 0.01). There was no effect of diet on semen volume, concentration or PLM of sperm when assessed either immediately following collection or post-thawing. Membrane fluidity and oxidative stress of sperm were also not affected by diet. The percentage of sperm with intact-acrosomes was lower in CTL bulls compared to those fed SO (P < 0.01). In conclusion, while the lipid composition of semen was altered following dietary supplementation with either n-6 or n-3 based PUFA, this did not lead to measurable improvements in the quantity or quality of semen produced by young post-pubertal dairy bulls.

Dietary Polyunsaturated Fatty Acid Supplementation Improves the Quality of Stallion Cryopreserved Semen

The objective was to assess the influence of polyunsaturated fatty acid supplementation on the quality of fresh, cooled, and frozen-thawed stallion semen. Ten stallions received their normal diet (control group) or normal diet plus 150 mL of polyunsaturated fatty acid (PUFA) linseed-based oil (PUFA group). Semen was collected every 15 days during 60 days. Stallions were reversed across the treatments after a sixty-day interval. Semen was evaluated at 2, 6, 12, and 24 hours after cooling and 24 hours after freezing. Motility (MOT), vigor, membrane viability, morphology, acrosome integrity, and osmotic tolerance test (OTT) were evaluated. In the frozen-thawed semen, sperm dynamic characteristics were analyzed by computer-assisted sperm analysis and thiobarbituric acid reactive substances (TBARs) determined. The effects of treatment, time, semen type, and their interactions were submitted to PROCMIX (SAS) and means compared by the Tukey test. There was no treatment effect on the quality of fresh and cooled semen. However, frozen-thawed semen MOT, vigor, and OTT were superior (P < .05) in control compared to PUFA group. An interactive effect of sample day by treatment was observed, such that, TBARs increased over time (P = .002) in the PUFA group after 15, 30, 45, and 60 days from the beginning of supplementation. Thus, sperm may become more susceptible to the reactive oxygen species, probably due to the incorporation of polyunsaturated fat in the cell membrane. The addition of PUFA-enriched oil may be an alternative for improving frozen-thawed semen quality by increasing its MOT and resistance to osmotic changes to which sperm cells are submitted during the freezing process.

Immune response, productivity and quality of milk from grazing goats as affected by dietary polyunsaturated fatty acid supplementation

This study was undertaken to assess how diet supplemented with fish oil and linseed improve the immune profile, the production performance, and milk quality of grazing goats by a diet supplementation of fish oil or linseed. Twenty-four Garganica grazing goats were divided into three groups named control (CON), fish oil (FO) and linseed (LIN) according to the fat supplement received in their diet. In vivo immune responses were evaluated by monitoring cell-mediated and humoral immune responses in order to verify the effects of polyunsaturated fatty acids supplementation on goats' health status. Goat milk samples were analysed weekly to determine milk chemical composition, fatty acid profile, and somatic cell count. Diet based on linseed supplementation (LIN) significantly increased milk yield by 30%, milk fat yield by 67%, protein yield by 34%, and casein yield by 41% as compared with CON. Fat content increased by 30% in LIN milk as compared with CON milk, and by 12% as compared with FO milk. Linseed modified milk fatty acid profile; LIN milk showed lower SFA and higher PUFA than FO milk. The modified fatty acid composition of LIN milk resulted in lower AI and TI indexes than FO and CON milk. Linseed and fish oil administration can reduce humoral immunity of goats, but has no effect in their cellular immunity. Dietary linseed supplementation in grazing dairy goat supports feeding programs to improve milk composition and quality, and a modulation of their immune responses.

Role of different sources of dietary PUFA supplementation on sheep welfare under high ambient temperature

The purpose of this study was to evaluate the effects of different sources of polyunsaturated fatty acids (PUFA) supplemented in the diet on the welfare of lactating sheep exposed to high ambient temperature. The experiment was conducted during summer, it involved 32 ewes divided into 4 groups, and lasted 6 weeks. All groups were fed twice daily and received 1.8kg/ewe/d of oat hay. The control group also received 1kg/ewe/d of pelleted concentrate, whereas ewes in the experimental groups were supplemented with whole flaxseed (FS), seaweed Ascophyllum nodosum (Tasco®, AG), or their combination (FS+AG). At the beginning of the experiment, and weekly thereafter, the respiration rate, rectal temperature, body condition score (BCS) and body weight of the ewes were recorded. Milk samples were collected from each ewe weekly for the determination of the chemical composition, somatic cell count, and coagulating properties. Milk samples were also analyzed for their concentration of plasmin. Flaxseed diet during heat stress resulted in a reduction of the respiration rate, and in an increase of both milk and fat yield. The PUFA in the combined diet influenced the rectal temperature, and the respiration rate; also the milk yield and the concentration of plasmin (PL) increased in FS+AG diet. The lowest value of BCS recorded in ewes receiving the AG diet together with a rise in the respiration rate and rectal temperature suggested poor sheep welfare. Furthermore, sheep receiving the AG diet showed a consistent increase in the milk PL concentration that was responsible of the increase of milk clotting time and rate of clot formation.

Omega-3 Fatty Acid Food Enrichment Influences Some Serum Acute Phase Proteins Concentration and White Blood Cell Count in Athlete Horses

The effect of exercise and dietary supplementation with polyunsaturated fatty acids (PUFAs) on serum amyloid A (SAA), fibrinogen (Fb), and white blood cell (WBC) count was studied in eight Italian Saddlebreds jumper and eight Thoroughbred horses. Horses were divided into four groups: two experimental groups including four jumpers (AJ) and four Thoroughbreds (AT) that received 4-week PUFAs supplementation and two control groups including four jumpers (BJ) and four Thoroughbreds (BT). Blood samples were collected before the starting of PUFAs supplementation at rest (T0R), 10 minutes (T0PE10), and 24 hours postexercise (T0PE24) and after PUFAs supplementation at rest (T1R), 10 minutes (T1PE10), and 24 hours postexercise (T1PE24). All horses showed a WBC increase after exercise (P < .0001). Higher Fb values were found in experimental groups than control groups at T1R, T1PE10, and T1PE24 (P < .005). Serum amyloid A values changed (P < .001) at T0R and T0PE10 vs. T0PE24 and at T1R and T1PE10 vs. T1PE24 in experimental and control groups. Higher SAA values were found in experimental groups than control groups at T1R, T1PE10, and T1PE24 (P < .005). Our findings showed that SAA concentration changed 24 hours after exercise, but it remains unchanged shortly after exercise. These results suggest that the evaluation of SAA immediately after exercise is not clinically useful and demonstrate that the intense exercise is able to induce an acute phase response although it is a noninflammatory condition. The significant effect of dietary PUFAs supplementation found on Fb and SAA levels emphases the PUFAs' property of modulating inflammation in jumper and Thoroughbred horses.

Embryonic development and growth performances of an endangered fish species Nandus nandus: effects of dietary polyunsaturated fatty acids supplementation

The present study explored the embryonic and larval development of an endangered fish species Nandus nandus and resolved larval growth performances with the dietary supplementation of different types of lipids. Fertilized eggs were collected from fiber glass tanks immediately after spontaneous spawning of N. nandus, which were fed with a 1% phospholipid (squid meal) supplemented diet for 3 months. Fertilized eggs were transparent, spherical, yellowish and sticky in nature. The first cleavages of eggs were observed 0.3±0.01 h post fertilization at 26 o C water temperature. Hatching started around 18 h post - fertilization and newly hatched larvae were found to be 1.2±0.1 mm in length. First feeding started 64.0±0.30 h post hatching. After rearing for 10 days, they were divided into 4 groups and separately fed with only dry tubificid worms, 1% docosahexaenoic (DHA) supplemented with dry tubificid worm, 1% phospholipid supplemented with dry tubificid worm and live tubificid worms as treatment I, treatment II, treatment III and treatment IV, respectively. After 50 days of the trial, larvae of treatment II showed significantly (p<0.01) higher growth performances in length: 3.18±0.13 cm, weight: 339.8 ± 36.94 mg and survival rate: 78±2 % which were comparable to that of treatment IV, which showed the highest (p<0.01) length of 3.4±0.1 cm, weight of 406.6±27.99 mg and survival rate of 97±1 %. Larvae in treatment I showed the lowest growth performances in length: 2.73 ± 0.16 cm, weight: 259.8±29.97 mg and survival rate of 63±3 %. As this is the first record for the determination of embryonic and larval development of N. nandus with different lipid supplemented diets, it might be possible to save this endangered fish species by adopting this technology at field level.

Increase in erythrocyte osmotic resistance following polyunsaturated fatty acids (PUFA) supplementation in show jumper horses

Osmotic fragility test has been used to study the influence of different factors on the osmotic properties of cell membranes. Considering the importance of polyunsaturated fatty acids (PUFA) in biological functions we aimed to investigate the effects of dietary PUFA supplementation on erythrocyte osmotic fragility (EOF), blood lactate (BL), hematocrit (Hct), red blood cell (RBC), hemoglobin (Hb), and mean cell volume (MCV) in 10 jumper horses. Two events occurred prior to start supplementing horse's diet and two events occurred after 4 weeks PUFA supplementation. Five horses received the PUFA supplementation (Group A), and five served as controls (Group B). Blood samples were taken before and after each course. The statistical analysis revealed significant increase in BL, Hct, RBC and Hb following exercise (P<0.0001). However, the interaction between exercise and PUFA supplementation (P=0.0083) showed PUFA-supplemented horses having a smaller rise in BL levels (P=0.0107) following exercise. Significant interactions between exercise and PUFA treatment were also found on EOF levels (P<0.05). The hemolysis curves showed PUFA-supplemented horses exhibiting a reduction in EOF compared to controls (P<0.05). Although hemolysis never occurred at 0.9% NaCl concentration, jumping exercise determined an increase in EOF (P=0.0014) at 0.8% NaCl solution. A significant interaction between exercise and PUFA treatment (P=0.0022) was found showing PUFA-supplemented horses having lower EOF (P=0.0015) following exercise. The assessment of EOF is a suitable indicator of athletic performance. The results showed that PUFA supplementation might exert beneficial effects on the horse body system by enhancing the performance in high-level show jumpers.

Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans

Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control (P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV (P < 0.001 for all). These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients.

How Selected Tissues of Lactating Holstein Cows Respond to Dietary Polyunsaturated Fatty Acid Supplementation

The effect of a 10-week supplementation with polyunsaturated fatty acids [via sunflower oil/DHA-rich algae (SUNA) or linseed oil/DHA-rich algae (LINA) enriched diets] versus saturated fatty acids (SAT) of lactating German Holstein dairy cows in mid-lactation on expression patterns of lipid metabolism-associated genes and gene products in hepatic, longissimus muscle and subcutaneous/perirenal/omental adipose tissue was assessed. Most pronounced transcriptomic responses to dietary PUFA were obtained in hepatic [down-regulated ACACA (FC=0.83, SUNA; FC=0.86, LINA), FADS1 (FC=0.60, SUNA; FC=0.72, LINA), FADS2 (FC=0.64, SUNA; FC=0.79, LINA), FASN (FC=0.64, SUNA; FC=0.72, LINA), SCD (FC=0.37, SUNA; FC=0.47, LINA) and SREBF1 (FC=0.79, SUNA, LINA) expression] and omental adipose [up-regulated ACACA (FC=1.58, SUNA; FC=1.22, LINA), ADFP (FC=1.33, SUNA; FC=1.32, LINA), CEBPA (FC=1.75, SUNA; FC=1.40, LINA), FASN (FC=1.57, SUNA; FC=1.21, LINA), LPL (FC=1.50, SUNA; FC=1.20, LINA), PPARG (FC=1.36, SUNA; FC=1.12, LINA), SCD (FC=1.41, SUNA; FC=1.17, LINA) and SREBF1 (FC=1.56, SUNA; FC=1.18, LINA) expression] tissue. Interestingly, gene/gene product associations were comparatively low in hepatic and omental adipose tissue compared with longissimus muscle, perirenal adipose and subcutaneous adipose tissue, indicating matches only in regard to minor concentrations of SCD product 18:1c9, FADS1 product 20:4n-6 and FADS2 product 18:3n-6 in hepatic tissue, and higher concentrations of ACACA and FASN gene products 12:0 and 14:0 and SCD product 18:2c9,t11 in omental adipose tissue. Whereas all analyzed tissues accumulated dietary PUFA and their ruminally generated biohydrogenation products, tissue-divergent preferences for certain fatty acids were identified. This descriptive study reports tissue-divergent effects of dietary PUFA and outlines the significance of a PUFA intervention with regard to dairy cows' nutritional management.

Effects of dietary polyunsaturated fatty acid supplementation on fatty acid composition in muscle and subcutaneous adipose tissue of lambs1

Lambs (n = 48) were used in a 2 x 2 factorial arrangement of treatments to evaluate effects of inclusion of oil containing PUFA in high-concentrate diets (with or without) and duration of oil supplementation (pre- vs. postweaning) on CLA concentration of muscle and adipose tissue. Lambs were fed preweaning creep diets (with or without oil) corresponding to the dietary lactation treatment diet (with or without oil) of the dam. Dams blocked by lambing date and rearing type were randomly assigned to 1 of 2 lactation dietary treatments with or without oil supplementation. Creep diets contained approximately 70% concentrate and 30% roughage and were provided to lambs for ad libitum intake. At weaning (58.7 +/- 2.5 d of age), lambs (n = 48) were randomly assigned within preweaning treatment groups to 1 of 2 postweaning dietary treatments (with or without oil) and 16 pens in a randomized block design, blocked by sex and BW. Postweaning diets were formulated to contain approximately 80% concentrate and 20% roughage and were fed once daily for ad libitum intake. Soybean and linseed oil (2:1, respectively) replaced ground corn and provided 3% additional fat in pre- and postweaning diets. Lambs were slaughtered at 60.3 +/- 4.2 kg of BW. A subcutaneous fat (SQ) sample was obtained within 1 h postmortem and a LM sample at the 12th rib was obtained 24 h postmortem, and both were analyzed for fatty acid profile. Feedlot performance and carcass measurements were not affected (P >or= 0.26) by oil supplementation. Total CLA content of LM and SQ was not affected (P >or= 0.08) by oil supplementation pre- or postweaning, but trans-10, cis-12 CLA was greater (P = 0.02) in SQ from lambs supplemented with oil postweaning. Total PUFA content in LM was greater (P = 0.02) in lambs supplemented with oil pre- or postweaning as a result of increased concentrations of 18:2cis-9, cis-12 and longer chain PUFA. Conversely, pre- and postweaning oil supplementation resulted in less (P = 0.04) MUFA content in LM. Only postweaning oil supplementation increased (P = 0.001) SQ PUFA content. Feeding oils containing PUFA to lambs pre- and postweaning did not increase CLA content of muscle, whereas postweaning oil supplementation minimally increased CLA concentration of SQ fat. Inclusion of soybean and linseed oil in pre- and postweaning diets increased total PUFA content of SQ fat and muscle tissue without adversely affecting growth performance or carcass characteristics.

Dietary n − 6 and n − 3 polyunsaturated fatty acids: From biochemistry to clinical implications in cardiovascular prevention

Linoleic acid (LA) and alpha linolenic acid (ALA) belong to the n − 6 (omega-6) and n − 3 (omega-3) series of polyunsaturated fatty acids (PUFA), respectively. They are defined “essential” fatty acids since they are not synthesized in the human body and are mostly obtained from the diet. Food sources of ALA and LA are most vegetable oils, cereals and walnuts. This review critically revises the most significant epidemiological and interventional studies on the cardioprotective activity of PUFAs, linking their biological functions to biochemistry and metabolism. In fact, a complex series of desaturation and elongation reactions acting in concert transform LA and ALA to their higher unsaturated derivatives: arachidonic acid (AA) from LA, eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) from ALA. EPA and DHA are abundantly present in fish and fish oil. AA and EPA are precursors of different classes of pro-inflammatory or anti-inflammatory eicosanoids, respectively, whose biological activities have been evoked to justify risks and benefits of PUFA consumption. The controversial origin and clinical role of the n − 6/ n − 3 ratio as a potential risk factor in cardiovascular diseases is also examined. This review highlights the important cardioprotective effect of n − 3 in the secondary prevention of sudden cardiac death due to arrhythmias, but suggests caution to recommend dietary supplementation of PUFAs to the general population, without considering, at the individual level, the intake of total energy and fats.

Influence of low-dose polyunsaturated fatty acids supplementation on the inflammatory response of healthy adults

Objective The aim of the present study was to examine the immune-modulating effect of two different fat blends enriched with a low dose of anti- or proinflammatory polyunsaturated fatty acids on the fatty acid status and subsequently on the immune response of healthy volunteers. Methods Thirty healthy volunteers were randomly assigned to group A (anti-inflammatory blend rich in polyunsaturated fatty acids: α-linolenic acid, 240 mg/d; eicosapentaenoic acid, 120 mg/d; stearidonic acid, 49 mg/d; and γ-linolenic acid, 73 mg/d) or group B (arachidonic acid, 40 mg/d; containing an inflammatory fat blend) for a 2-wk dietary supplementation period. Concentrations of interleukin-8, interleukin-10, tumor necrosis factor-α, prostaglandins E 1 and E 2, and leukotriene B 4 were investigated before, after 2 wk of supplementation, and 2 wk after stopping supplementation using a whole blood ex vivo lipopolysaccharide-stimulation assay. Results Plasma concentrations of α-linolenic acid and eicosapentaenoic acid were significantly increased in group A. In addition, dietary fat blends influenced eicosapentaenoic acid concentration in erythrocyte membranes. Supplementation of the fat blends resulted in contrasting effects on the expression of lipid mediators and cytokines after ex vivo lipopolysaccharide stimulation. Release of prostaglandin E 1 and leukotriene B 4 were significantly decreased in group A, whereas prostaglandin E 2 and interleukin-10 concentrations were significantly increased in group B. No effect on interleukin-8 or tumor necrosis factor-α release was found after supplementation with either fat blend. Conclusions These results show an immune-modulating effect of a low-dose dietary polyunsaturated fatty acid supplementation. However, further studies regarding fat-blend composition and period of supplementation in patients with inflammatory conditions are required.

Immunosuppressive effects of polyunsaturated fatty acids on antigen presentation by human leukocyte antigen class I molecules

Dietary supplementation with polyunsaturated fatty acids (PUFAs) has immunosuppressive effects; however, the molecular targets of PUFAs and their mode of action remain unclear. One possible target is antigen presentation to T cells through the human leukocyte antigen (HLA) class I pathway. Here we show that incorporation of PUFAs lowers target cell susceptibility to lysis by effector T cells. Treatment of B lymphoblast targets with the omega-6 PUFA arachidonic acid (AA) or omega-3 docosahexaenoic acid lowered their susceptibility to lysis by alloreactive CD8+ T cells by approximately 20-25%. HLA class I surface levels and their rate of endoplasmic reticulum (ER)-Golgi traffic were also reduced by PUFA treatment. Calibration experiments showed that the approximately 15% reduction in surface HLA I was not sufficient to completely account for the decreased lysis. However, PUFAs significantly lowered antigen-presenting cell-T cell conjugate formation, by approximately 30-40%. Taken together, our data show for the first time that an omega-6 and an omega-3 PUFA affect the HLA class I pathway of B lymphoblasts. Our findings suggest that elimination of self- and pathogen-derived peptides by effectors may be compromised by dietary PUFA supplementation. In addition, PUFA-mediated changes in ER-Golgi trafficking point to a new area of PUFA modulation of immune responses.

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The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha “spontaneous” baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from −0.09 ± 0.01 to −0.16 ± 0.01 mm Hg · mm Hg−1, p < 0.01, and from 1.25 ± 0.9 to 1.76 ± 1.1 ms · mm Hg−1, p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 ± 1.4 to 12.2 ± 1.2 ms · mm Hg−1, p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.