Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

Background The placenta plays a crucial role in supporting and influencing fetal development.We compared the effects of prepartum supplementation with omega-3(n-3)fatty acid(FA)sources,flaxseed oil(FLX)and fish oil(FO),on the expression of genes and proteins related to lipid metabolism,inflammation,oxidative stress,and the endocannabinoid system(ECS)in the expelled placenta,as well as on FA profile and inflammatory response of neonates.Late-pregnant Holstein dairy cows were supplemented with saturated fat(CTL),FLX,or FO.Placental cotyledons(n=5)were collected immediately after expulsion,and extracted RNA and proteins were analyzed by RTPCR and proteomic analysis.Neonatal blood was assessed for FA composition and concentrations of inflammatory markers.Results FO increased the gene expression of fatty acid binding protein 4(FABP4),interleukin 10(IL-10),catalase(CAT),cannabinoid receptor 1(CNR1),and cannabinoid receptor 2(CNR2)compared with CTL placenta.Gene expression of ECS-enzyme FA-amide hydrolase(FAAH)was lower in FLX and FO than in CTL.Proteomic analysis identified 3,974 proteins;of these,51–59 were differentially abundant between treatments(P≤0.05,|fold change|≥1.5).Top canonical pathways enriched in FLX vs.CTL and in FO vs.CTL were triglyceride metabolism and inflammatory processes.Both n-3 FA increased the placental abundance of FA binding proteins(FABPs)3 and 7.The abundance of CNR1 cannabinoid-receptor-interacting-protein-1(CNRIP1)was reduced in FO vs.FLX.In silico modeling affirmed that bovine FABPs bind to endocannabinoids.The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1,whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs.CTL placenta.Maternal FO enriched neonatal plasma with n-3 FAs,and both FLX and FO reduced interleukin-6 concentrations compared with CTL.Conclusion Maternal n-3 FA from FLX and FO differentially affected the bovine placenta;both enhanced lipid metabolism and modulated oxidative stress,however,FO increased some transcriptional ECS components,possibly related to the increased FABPs.Maternal FO induced a unique balance of pro-and anti-inflammatory components in the placenta.Taken together,different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes,which may affect the neonatal immune system.

Branched-chain fatty acids from goat milk alleviate ulcerative colitis via the TLR4/NF-κB/NLRP3 pathway

Branched-chain fatty acids(BCFAs)are new bioactive fatty acids with anti-inflammatory properties.However,the role of BCFAs in alleviating ulcerative colitis has not been clarified.Herein,we evaluated the protective effect of BCFAs from goat milk in mice with colitis induced using dextran sodium sulfate(DSS)and explored the corresponding mechanism.These results show that BCFAs extracted from goat milk can significantly alleviate weight loss in mice,and reduce the disease activity index and the activity of myeloperoxidase while increasing the content of antioxidant enzymes in colon tissue and reducing the oxidation stress response.These data also show that BCFAs can down-regulate the gene and protein expression of the toll-like receptor 4(TLR4)/nuclear factorκB p65(NF-κB p65)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,and at the same time significantly reduce the expression of pro-inflammatory factors tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β),and IL-18 in colon tissue,and significantly increase the expression of the anti-inflammatory factor IL-10.In conclusion,these results demonstrated that BCFAs in goat milk exerted effects on colitis-related inflammatory cytokines and inhibited inflammation by inducing the TLR4/NF-κB/NLRP3 pathway to alleviate DSS-induced ulcerative colitis.This study provides evidence for the potential of BCFAs as bioactive fatty acids in food products and to ameliorate ulcerative colitis development in mice.

Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation

AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.

Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients

AIM: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients. METHODS: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study. Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid, Fresenius-Kabi, SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven, Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated. Routine blood test, biochemistry, systemic levels of IL-6 and TNF-α, percentage of CD3+, CD4+, and CD8+ lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length of postoperative hospital stay, and occurrence of infectious complications. RESULTS: Both lipid regimens were well tolerated. No differences between the two groups were noticed in demographics, baseline blood test, biochemistry, serum levels of IL-6 and TNF-α, percentage of CD4+, CD8+ lymphocytes, and ratios of CD4+/CD8+. Compared with those on postoperative d 1, serum IL-6 levels onpostoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 ± 30.53 vs -8.39 ± 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD8+ were significantly increased in the FO group (0.92 ± 0.62 vs 0.25 ± 1.22, P = 0.035). In addition, depression of serum TNF-α levels (-0.82 ± 2.71 vs 0.27 ± 1.67, P = 0.125) and elevation of CD3+ and CD4+ lymphocyte percentage (12.85 ± 11.61 vs 3.84 ± 19.62, P = 0.081, 17.80 ± 10.86 vs 9.66 ± 17.55, P = 0.084, respectively) were higher in the FO group than in the reference group. Patients in the FO group trended to need a shorter postoperative hospital stay (17.45 ± 4.80 d vs 19.62 ± 5.59 d, P = 0.19). No statistically significant difference was found when stratified to mortality and occurrence of infectious complications. CONCLUSION: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radical resection by lowering the magnitude of inflammatory responses and modulating the immune response.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome

AIM:To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome.METHODS:A prospective,interventional,placebo controlled,double blind randomized trial was done at two referral eye centers.Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule(500mg)two times a day containing 325mg EPA and 175mg DHA for 3 months(omega-3 group).The omega-3 group was compared to a group of patients(n=254)who received a placebo(placebo group).There were 4 patient visits(at baseline,1 month,2 months and3 months).On each visit,recording of corrected distance visual acuity(CDVA),slit lamp examination and questionnaire based symptom evaluation and scoring was done.A symptomatic score of 0-6 was mild,6.1-12moderate and 12.1-18 severe dry eye.Response to intervention was monitored by routine tear function tests like Schirmer I test,tear film break-up time(TBUT),Rose Bengal staining and most notably,conjunctival impression cytology.RESULTS:Sixty-five percent of patients in the omega-3group and 33%of patients in placebo group had significant improvement in symptoms at 3 months(P=0.005).There was a significant change in both Schirmer’s test value and TBUT values in the omega-3group(P【0.001),both comparisons.However,there was a larger drift in TBUT values in omega-3 than the placebo group,in comparison to Schirmer’s test values.The mean TBUT score was 2.54±2.34 in the omega-3group and 0.13±0.16 in placebo group,respectively.The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebogroup(P【0.001).Despite a slight increase mean score,the Schirmer scores did not correlate well with symptomatic improvement.CONCLUSION:Omega-3 fatty acids have a definite role for dry eye syndrome.The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease.The role of omega fatty acids in tear production and secretion needs further evaluation.

Anti-inflammatory and Immunomodulatory Effects of Marine n-3 Polyunsaturated Fatty Acids on Human Health and Diseases

The pharmaceutical effects of n-3 polyunsaturated fatty acids(n-3 PUFAs) as dietary nutrients on human health and diseases have gained much attention and are investigated for decades. Docosahexaenoic acid(DHA), eicosapentaenoic acid(EPA) and docosapentaenoic acid(DPA) are the three major n-3 PUFAs enriched in marine organisms, such as fish, shrimp, algae, and so on. It has been well known that n-3 PUFAs, especially DHA and EPA, are beneficial in reducing the risk of cardiovascular and cerebrovascular diseases. Accumulating evidence suggests that n-3 PUFAs might cure inflammatory diseases through several mechanisms, such as plasma membrane remodeling of lymphocytes, down-regulating pro-inflammatory cytokines, and alternating adhesion molecule expressions. Several molecular targets of n-3 PUFAs on immune-regulation have also been identified, such as GPR120(FFA4), protein kinase C(PKC), and PPAR-γ. However, it remains inconclusive if dietary n-3 PUFAs function the same both in vitro and in vivo based on cohort studies. This review will focus on the molecular targets and mechanisms of anti-inflammatory and immunomodulatory effects of n-3 PUFAs on human health and diseases, such as obesity, tumor, diabetes, and autoimmune diseases.

Transgenic Pigs Carrying a Synthesized Fatty Acid Desaturase Gene Yield High Level of ω-3 PUFAs

Polyunsaturated fatty acids （PUFAs） are essential for normal growth in mammals, especially the ω-3 PUFAs, which play important roles in preventing several life-threatening diseases, such as coronary heart disease and diabetes. In this study, we aimed to investigate whether the sFat-1 gene from Caenorhabditis briggsae could be functionally expressed in transgenic pigs, and whether the transgenic could synthesize high quality ω-3 PUFAs endogenously. In this study, a gene construct consisting of CMV promoter and 1.9 kb cDNA of ω-3 fatty acid desaturase gene （sFat-1） from C. briggsae was injected into the male pronucleus of pig embryos by microinjection. The piglets were screened for the transgene by PCR, Southern blot and reverse transcription-PCR analysis. Pigs that give positive results were mated with wild-type pigs to produce the next generation and the transmission of transgene was examined by PCR analysis. Fatty acids compositions of various tissues in the transgenic pigs were then analyzed by gas chromatograph. A total of 878 embryos were transferred into 42 recipients, among which 29 successfully got pregnant and gave birth to a total of 162 piglets, and 8 of them were identified to be transgenic. Fatty acid compositions in the transgenic pigs were altered, and the levels of ω-6：ω-3 ratios were decreased from 14.53 in the control to 2.62 in Fat-1 transgenic pigs. A number of primary sFat-1-transgenic pigs were bred in this study, which lays the foundation for cultivation of new varieties of transgenic pigs.

Effects of dietary ratio of n-6 to n-3 polyunsaturated fatty acids on immunoglobulins, cytokines, fatty acid composition, and performance of lactating sows and suckling piglets

This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning （26-29 d） and were fed diets containing different ratios of n-6：n-3 PUFA including 3：1,9：1 and 13：1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation （P 〉 0.05）. Litter size at d 14 and d 21 were tended to increase in 3：1 treatment compared with 9：1 and 13：1 treatments （P 〈 0.10）. Litter weight gain （1.77 kg/d） from d 0 to d 14 was tended to increase in 9：1 groups compared with the other two treatments （P 〈 0.10）. A significant difference was observed for the content of a -linolenic acid, total n-3 PUFA, and the ratio of n-6：n-3 PUFA in the colostrum, milk, and piglets plasma （P 〈 0.01）. The effects of different ratios of n-6：n-3 PUFA in sow diets on colostrum, milk and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum （P 〉 0.05）. A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM （P〈 0.01） concentrations in piglet plasma at d14 and a significant difference for IgG（P 〈 0.05） was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3：1 compared with 13：1 group （P 〈 0.01）. In summary, the current study demonstrated that altering the ratio of n-6：n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average daily gain and improve the immune status of piglets when dietary ratio of n-6：n-3 PUFA was 9：1.

Omega-3 fatty acid improves the clinical outcome of hepatectomized patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma

Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV- associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive stand- ard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutri- tion (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection- related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P 〈 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23__+ 18.48 U/L vs control, 73.34 q-40.60 U/L, P 〈 0.01), aspartate transaminase (omega-3 fatty acid, 35.77_ 14.56 U/L vs control, 50.53 4-24.62 U/L, P 〈 0.01), total bilirubin (omega-3 fatty acid, 24.29___7.40 mmol/L vs control, 28. 374-8.06 mmol/L, P 〈 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71 ___2.58 d vs control, 15.91 ___3.23 d, P 〈 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98___5.63 pg/mL vs control, 35.55___7.5 pg/mL, P 〈 0.01) and TNF-a (ome- ga-3 fatty acid, 4.43___1.22 pg/mL vs control, 5.96___1.58 pg/mL, P 〈 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients.

Recent advances in liver preconditioning: Thyroid hormone, n-3 long-chain polyunsaturated fatty acids and iron

Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.

Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats

AIM:To evaluate the effectiveness of omega-3 polyunsaturated fatty acid(ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy(PH) in rats.METHODS:ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery.PH,sparing only the caudate lobe,was performed in both the control and the ω-3 PUFA group.Survival rates,liver weight/body weight ratios,liver weights,HE staining,transmission electron microscope imaging,nuclearassociated antigen Ki-67,enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration.RESULTS:All rats in the control group died within 30 h after hepatectomy.Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH.Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group.The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH.In the ω-3 PUFA group,interleukin(IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-levels were dramatically decreased.In addition,activation of protein kinase B(Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group.CONCLUSION:Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Usefulness of ω-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: A double-blind, randomized, placebo-controlled study

AIM： To assess the value of long-chain w-3 fatty acids （FAs） supplementation in addition to amino-salicylic-acid （5-ASA） in pediatric patients with Crohn＇s disease （CD）. METHODS： Thirty-eight patients （20 males and 18 females, mean age 10.13 years, range 5-16 years） with CD in remission were randomized into two groups and treated for 12 too. Group Ⅰ （18 patients） received 5-ASA （50 mg/kg/d）＋w-3 FAs as triglycerides in gastroresistant capsules, 3 g/d （eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g）. Group Ⅱ （20 patients） received 5-ASA （50 mg/kg/d）＋olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS： The number of patients who relapsed at 1 year was significantly lower in group I than in group Ⅱ （P〈0.001）. Patients in group I had a significant increase in the incorporation of EPA and DHA （P〈0.001） and a decrease in the presence of arachidonic acids. CONCLUSION： Enteric-coated w-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD.

Effects of the Ratio of n-6∶n-3 Polyunsaturated Fatty Acids in the Maternal Diet on Immunoglobulins,Fatty Acid Composition,and Performance of Lactating Sows and Suckling Piglets under Conditions of Low Maternal Energy Intake

This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible energy intakes. Twenty-one pregnant Landrace sows were assigned to one of three diets from day 108 of gestation until weaning （26 to 29 d） ,containing n-6∶n-3 PUFA ratios of 3 ∶1,8 ∶1 and 11 ∶1. The effects on sow and litter production traits and on sow body condition were examined. There were no differences among treatments in daily feed intakes or in changes in sow weight and back-fat levels during lactation. Litter size,litter weight at birth and weaning and litter average daily weight gain were also unaffected by treatment. As expected, large differences were observed in n-6 and n-3 fatty acids in the colostrum and plasma of sows and piglets （P 〈 0. 01） . The ratio of n6 ∶ n-3 PUFA the diet was positively correlated with those in colostrum,sow plasma and piglet plasma （R 2= 0. 55,0. 80 and 0. 80,respectively） . Sow plasma insulin and IGF-I levels at weaning were unaffected by the treatments. Plasma leptin （P 〈 0. 05） concentrations were increased in sows fed the diet with a n-6∶n-3 ratio of 8 ∶ 1. Immunoglobulin concentrations in colostrum were not altered by dietary treatment. Plasma IgG concentrations at d 14 were highest in piglets from sows fed the 8 ∶ 1 ratio of n-6∶n-3. Furthermore,this group had the highest IgA concentrations at day 21 of lactation compared with the other two groups （P 〈 0. 05） . In summary,our study demonstrated that at low digestible energy levels,altering the ratio of n-6 ∶ n-3 PUFA in the diets for lactating sows affected immune components and the fatty acid composition of lactating sows and their piglets. Further studies are needed to examine whether higher levels of fat supplementation than those used in the present study （1. 5%） can successfully enhance performance.

Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation:Mechanisms and implications for psychopathology

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

Effect of ω-3 Polyunsaturated Fatty Acid on Toll-like Receptors in Patients with Severe Multiple Trauma

This study examined the effects of ω-3 polyunsaturated fatty acid（ω-3PUFA） on the expression of toll-like receptor 2（TLR2）,toll-like receptor 4（TLR4） and some related inflammatory factors in peripheral blood mononuclear cells（PBMCs） of patients with early-stage severe multiple trauma.Thirty-two patients who were admitted to the Department of Traumatic Surgery,Tongji Hospital（Wuhan,China） between May 2010 and November 2010,and diagnosed as having severe multiple trauma with a injury severity score（ISS） no less than 16,were enrolled in the study and divided into two groups at random（n=16 in each）：ω-3PUFA group and control group in which routine parenteral nutrition supplemented with ω-3PUFA or not was administered to the patients in two groups for consecutive 7 days.Peripheral blood from these patients was collected within 2 h of admission（day 0）,and 1,3,5 and 7 days after the nutritional support.PBMCs were isolated and used for detection of the mRNA and protein expression of TLR2 and TLR4 by using real-time PCR and flow cytometry respectively,the levels of NF-κB by quantum dots-based immunofluorescence assay,the levels of TNF-α,IL-2,IL-6 and COX-2 by ELISA,respectively.The results showed that the mRNA and protein expression of TLR2 and TLR4 in PBMCs was significantly lower in ω-3PUFA group than in control group 5 and 7 days after nutrition support（both P0.05）.The levels of TNF-α,IL-2,IL-6 and COX-2 were found to be substantially decreased in PBMCs in ω-3PUFA group as compared with control group at 5th and 7th day（P0.05 for all）.It was concluded that ω-3PUFA can remarkably decrease the expression of TLR2,TLR4 and some related inflammatory factors in NF-κB signaling pathway in PBMCs of patients with severe multiple trauma,which suggests that ω-3PUFA may suppress the excessive inflammatory response meditated by the TLRs/NF-κB signaling pathway.

Role of omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes on intestinal barrier integrity and immunity in animals

The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.

A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle

Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids(FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study(GWAS) on milk FAs in dairy cattle, 83 genomewide significant single nucleotide polymorphisms(SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18 index(P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3000 bp of 5′ and 3′ regulatory regions of the AGPA T3 gene, a total of 17 SNPs were identified, including four in 5′ regulatory region, one in 5′ untranslated region(UTR),three in introns, one in 3′ UTR, and eight in 3′ regulatory region. By the linkage disequilibrium(LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs,respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0(P < 0.0001–0.0384). Further, with Genomatix, we predicted that four SNPs in 5′ regulatory region(g.146702957 G > A, g.146704373 A > G, g.146704618 A > G and g.146704699 G > A) changed the transcription factor binding sites(TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373 A > G and g.146704618 A > G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G(P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.

Different n-6/n-3 polyunsaturated fatty acid ratios affect postprandial metabolism in normal and hypertriglyceridemic rats

Postprandial metabolism plays major roles in many pathological conditions.The n-6/n-3 polyunsaturated fatty acid(PUFA)ratio is closely related to various physiological disorders.This study aimed to investigate the effects of high fat meals with different n-6/n-3 PUFA ratios on postprandial metabolism in normal control(NC)and hypertriglyceridemia(HTG)rats.The postprandial response of triglyceride(TG)in HTG groups was higher than that in NC groups after different n-6/n-3 PUFA ratio meals.The HTG groups showed higher postprandial total cholesterol(TC)responses than NC groups after 1:1 and 20:1 ratio meals.The 5:1 n-6/n-3 PUFA ratio elicited lower postprandial responses of tumor necrosis factorα(TNF-α)than 1:1 and 10:1 ratios in HTG groups.The postprandial malondialdehyde(MDA)response was lower after a 5:1 n-6/n-3 PUFA ratio meal than 1:1 and 20:1 ratio meals in HTG groups.The 1:1 ratio resulted in a lower postprandial reactive oxygen species(ROS)level than 5:1 and 10:1 n-6/n-3 PUFA ratios in NC groups.The results showed that a low n-6/n-3 PUFA ratio improved postprandial dysmetabolism induced by a high fat meal in NC and HTG rats.A high n-6/n-3 PUFA ratio increased the difference in postprandial metabolism between NC and HTG rats.