Endogenous biosynthesis of docosahexaenoic acid(DHA)regulates fish oocyte maturation by promoting pregnenolone production

Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related to this phenomenon remains largely unknown.In this study,we employed two zebrafish genetic models,i.e.,elovl2^(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3 desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and quality.Results show that the elovl2^(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls.DHA deficiency in elovl2^(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone levels.Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during oogenesis.In turn,the hypothalamic-pituitary-gonadal axis was enhanced by DHA.In conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.

Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

AIM: To explore the synergistic effect of docosahexaenoic acid(DHA)/5-fluorouracil(5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h. To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology. Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes(METCs)?Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis. RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner. DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-fold in an apparent synergy. The morphological changes of the cells were characterized by shrinkage, cell membrane blebbing and decreased adherence. Cell cycle analysis showed a shift of cells into the G0/G1 phase from the S phase following treatment with DHA or 5-FU(G0/G1 phase: 30.04% ± 1.54% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 56.76% ± 3.14% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). Combination treatment of DHA and 5-FU resulted in a significantly larger shift toward the G0/G1 phase and subsequent reduction in S phase(G0/G1 phase: 69.06% ± 2.63% vs 49.05% ± 6.41% and 63.39% ± 6.83%, respectively, P < 0.05; S phase: 19.80% ± 4.30% vs 34.75% ± 2.35% and 25.63% ± 2.21%, respectively, P < 0.05). This synergy was also reflected in the significant downregulation of the expression of METCs in AGS cells.CONCLUSION: Synergistic anticancer properties of DHA and 5-FU may involve interference with energy production of AGS cells via downregulation of METCs and cell cycle arrest.

Long-Term Effects of Docosahexaenoic Acid-Bound Phospholipids and the Combination of Docosahexaenoic Acid-Bound Triglyceride and Egg Yolk Phospholipid on Lipid Metabolism in Mice

The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(PL-DHA), and the combination of TG-DHA and egg yolk phospholipid(Egg-PL) on lipid metabolism in mice fed with a high-fat diet(fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat(HF) group(P < 0.05). Atherogenic index(AI) of the PL-DHA group was significantly lower than that of the combination group(P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group(P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group(P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA(0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.

High Sn-2 Docosahexaenoic Acid Lipids for Brain Benefits, and Their Enzymatic Syntheses: A Review

The normal development and maintenance of central neural functions are highly correlated with the amount of docosahexaenoic acid(DHA;ω-3 fatty acid)accumulated in the brain.DHA incorporated at the sn-2 position of lipids is well absorbed by intestinal mucosa and utilized efficiently in vivo.However,modern consumers have a reduced direct intake of DHA and increased intake of saturated fats or ω-6 fatty acid oils,resulting in behavioral and neurophysiological deficits.To provide an understanding of the integrated beneficial effects of DHA on the human brain,this review introduces the positional difference(sn-2 and sn-1,3 positions)of DHA on a glycerol skeleton in natural fats and oils,and further discusses the possible functional mechanism regarding DHA supplementation and the gut-brain axis.The multiple bidirectional routes in this axis offer a novel insight into the interaction between DHA supplementation,the gut microbiota,and brain health.To achieve high sn-2 DHA in diets,it is suggested that sn-2 DHA lipids be enzymatically produced in more efficient and economical ways by improving the specific activities of lipases and optimizing the purification procedures.These types of diets will benefit individuals with strong needs for sn-2 ω-3 lipids such as infants,children,and pregnant and lactating women.

Effect of docosahexaenoic acid on the recovery of motor function in rats with spinal cord injury: a meta-analysis

Objective:Studies have shown that docosahexaenoic acid(DHA)has a beneficial effect in the treatment of spinal cord injury.A meta-analysis was used to study the effect of DHA on the neurological recovery in the rat spinal cord injury model,and the relationship between the recovery of motor function after spinal cord injury and the time and method of administration and the dose of DHA.Data source:Published studies on the effect of DHA on spinal cord injury animal models from seven databases were searched from their inception to January 2019,including PubMed,MEDLINE,EMBASE,the China National Knowledge Infrastructure,Wanfang,VIP,and SinoMed databases.The search terms included“spinal cord injury”“docosahexaenoic acid”,and“rats”.Data selection:Studies that evaluated the influence of DHA in rat models of spinal cord injury for locomotor functional recovery were included.The intervention group included any form of DHA treatment and the control group included treatment with normal saline,vehicle solution or no treatment.The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias assessment tool was used for the quality assessment of the included studies.Literature inclusion,quality evaluation and data extraction were performed by two researchers.Meta-analysis was then conducted on all studies that met the inclusion criteria.Statistical analysis was performed on the data using RevMan 5.1.2.software.Outcome measures:The primary outcome measure was the score on the Basso,Beattie,and Bresnahan scale.Secondary outcome measures were the sloping plate test,balance beam test,stair test and grid exploration test.Results:A total of 12 related studies were included,3 of which were of higher quality and the remaining 9 were of lower quality.The highest mean Basso,Beattie,and Bresnahan scale score occurred at 42 days after DHA treatment in spinal cord injury rats.At 21 days after treatment,the mean difference in Basso,Beattie,Bresnahan scores between the DHA group and the control group was the most significant(pooled MD=4.14;95%CI=3.58–4.70;P<0.00001).In the subgroup analysis,improvement in the Basso,Beattie,and Bresnahan scale score was more significant in rats administered DHA intravenously(pooled MD=2.74;95%CI=1.41–4.07;P<0.0001)and subcutaneously(pooled MD=2.99;95%CI=2.29–3.69;P<0.00001)than in the groups administered DHA orally(pooled MD=3.04;95%CI=–1.01 to 7.09;P=0.14).Intravenous injection of DHA at 250 nmol/kg(pooled MD=2.94;95%CI=2.47–3.41;P<0.00001]and 1000 nmol/kg[pooled MD=3.60;95%CI=2.66–4.54;P<0.00001)significantly improved the Basso,Beattie,and Bresnahan scale score in rats and promoted the recovery of motor function.Conclusion:DHA can promote motor functional recovery after spinal cord injury in rats.The administration of DHA by intravenous or subcutaneous injection is more effective than oral administration of DHA.Intravenous injection of DHA at doses of 250 nmol/kg or 1000 nmol/kg is beneficial.Because of the small number and the low quality of the included studies,more high-quality research is needed in future to substantiate the results.

Moderating effect of synthesized docosahexaenoic acid-enriched phosphatidylcholine on production of Th1 and Th2 cytokine in lipopolysaccharide-induced inflammation

Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Amyloid β(Aβ)1-42 fibrillation is a crucial step in the development of pathological hallmarks, such as neuritic plaques and neurofibrillary tangles, of Alzheimer’s disease (AD). In this study, we evaluated the effects of free docosahexaenoic acid (DHA), an essential brain polyunsaturated fatty acid (PUFA), on the inhibition of Aβ1-42 fibrillation by fluorescence correlation spectroscopy (FCS), a technique capable of detecting molecular movements and interactions in solution. We also examined whether free arachidonic acid (AA), eicosapentaenoic acid (EPA), and metabolites of DHA, including neuroprotectin D1 (NPD1, 10S, 17S-dihydroxy-DHA), resolvin D1 (RvD1, 7S, 8R, 17S-trihydroxy-DHA), and didocosahexaenoyl glycerol (diDHA), affect Aβ1-42 polymerization. The results of the FCS study reveal that DHA and AA significantly reduced the diffusion time of TAMRA (5-carboxytetramethylrhoda-mine)-Aβ1-42 by 28% and 31%, respectively, while EPA, NPD1, RvD1, and diDHA had no effects on diffusion time. These results indicate that DHA and AA inhibited Aβ1-42 polymerization and that their inhibitory effects occurred at the initial stage of Aβ1-42 polymerization. This study will advance the research on PUFAs in preventing AD progression.

Large-Scale Production of Microalgal Lipids Containing High Levels of Docosahexaenoic Acid upon Fermentation of <i>Aurantiochytrium</i>sp. KRS101

In this study, large-scale production of microalgal lipid containing high levels of docosahexaenoic acid (DHA) by fermentation of Aurantiochytrium sp. KRS101 was performed. The microalgal strain yielded productivity of docosahex-aenoic acid (DHA) productivity of 1.08 and 1.6 g/L/d by fermentation at 300-L and 5000-L scale stirrer-type bioreactor. The productivity was significantly enhanced upto 5.6 g/L/d by fermentation at 6000-L scale airlift-type bioreactor, probably due to the reduced shearing force. The microalgal lipid could be efficiently recovered by safe extraction methods such as ethanol extraction, hot water extraction or supercritical fluid extraction, promising commercial potential of the microalgal DHA-rich lipid in the food and feed industry.

Docosahexaenoic Acid in Breast Milk Reflects Maternal Fish Intake in Iranian Mothers

To estimate essential fatty acid (FA) and long-chain polyunsaturated fatty acid (LCPUFA) concentrations in early breast milk (BM) in relation to habitual fish intake. BM was collected within 72-hours after delivery from consecutively included mothers, 60 in Guilan (coastal) and 60 in Kermanshah (inland) provinces. Mothers were interviewed to com-plete a food frequency questionnaire. The FA composition was measured with gas chromatography. Mothers in the coastal area had higher intake of fish/seafood. Consumption of saturated fat was higher in Kermanshah and olive intake was higher in Guilan. High fish/seafood intake was associated with higher docosahexaenoic acid (DHA) and lower arachidonic acid (AA)/DHA ratio in BM. There were no differences in linoleic and α-linolenic acid concentrations in BM between the provinces. N-3 FA and DHA concentration were significantly higher in Guilan than Kermanshah, but total n-6 FAs and AA did not differ and were high in both provinces. The ratios of total n-6/n-3 and AA/DHA in BM of mothers from Guilan were significantly lower than those in Kermanshah. The LCPUFA status in BM in two Iranian provinces was generally good and DHA was higher and the AA/DHA was significantly lower in mothers with high fish intake.

Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

AIM： To investigate the impact of arachidonic acid （AA） and docosahexaenoic acid （DHA） and their combination on colon cancer cell growth. METHODS： The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 （COX-2）, p21 and bcl-2 in ceils incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 （PGE2） generation in the presence of AA and DHA was measured using a PGE2- ELISA. RESULTS： AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dosedependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly, DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner. CONCLUSION： These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

Docosahexaenoic acid-rich fish oil prevented insulin resistance by modulating gut microbiome and promoting colonic peptide YY expression in diet-induced obesity mice

It is unclear how docosahexaenoic acid(DHA)improves insulin resistance via modulating gut microbiome in obese individuals.We used diet-induced obesity(DIO)mice as a model to study the effects of DHA-rich fish oil(DHA-FO)on host metabolic disorders and colonic microbiome.DHA-FO reduced fat deposition,regulated lipid profiles and alleviated insulin resistance in DIO mice.Probably because DHA-FO prevented the permeation of lipopolysaccharide across intestinal epithelial barrier,and promoted peptide YY(PYY)secretion via the mediation of short chain fatty acids receptor(FFAR2)in colon.Furthermore,DHA-FO might regulate PYY expression by reversing microbial dysbiosis,including increasing the abundance ofAkkermansia muciniphila and Lactobacillus,and suppressing the growth of Helicobacter.DHA-FO also altered gut microbial function(e.g."linoleic acid metabolism")associated with PYY expression(r>0.80,P<0.05).Herein,DHA-FO enhanced insulin action on glucose metabolism by altering gut microbiome and facilitating colonic PYY expression in DIO mice.

Protective effects of docosahexaenoic acid against non-alcoholic hepatic steatosis through activating of JAK2/STAT3 signaling pathway

Non-alcoholic fatty liver disease is the most common cause of hepatic dysfunction.In the present study,human normal hepatocyte L02 cells were treated with 50%fetal bovine serum to induce the formation of hepatic steatosis in vitro,and then the cells were treated with docosahexaenoic acid to investigate its protective effect on Non-alcoholic fatty liver disease.Our results showed that 50%of fetal bovine serum significantly induced intracellular lipid accumulation and hepatocyte fatty degeneration within 48 h.The expression level of adipose formation-related genes was significantly up-regulated,such as PPARγ,C/EBPαand SREBP-1;meanwhile,the content of cellular total lipid,total cholesterol and triglycerides were significantly increased after 50%fetal bovine serum treatment.Interestingly,docosahexaenoic acid treatment could inhibit FBS-induced intracellular lipid accumulation in L02 cells and the expression of lipogenic genes.Moreover,docosahexaenoic acid treatment could reduce hepatic steatosis-induced oxidative stress and endoplasmic reticulum stress response,and these responses were shown by the modification of antioxidant enzyme activities and GRP78,CHOP expression.In addition,the results showed that docosahexaenoic acid can activate the JAK2/STAT3 signaling pathway in fatty liver L02 cell;inhibition of JAK2/STAT3 signaling pathway by WP1066 abolished the beneficial effects of docosahexaenoic acid on hepatic steatosis accompanied with the increased expression of lipogenic genes and endoplasmic reticulum stress response.Above all,the present study showed that docosahexaenoic acid can alleviate non-alcoholic hepatic steatosis by activating JAK2/STAT3 signaling pathway.

Fortification of pork loins with docosahexaenoic acid(DHA) and its effect on flavour

Pork is traditionally low in docosahexanoic acid （DHA, C22：6n-3） and deficient in omega-3 fats for a balanced human diet. DHA as triglycerides was commercially prepared from the microalgae Schizochytfium and injected into fresh pork loins. Treatments of a mixed brine control （CON）, 3.1% sunflower oil in mixed brine （SF） and a 3.1% DHA oil in mixed brine （DHA） were injected into pork loins at 10 mL/100 g and grilled at 205℃. After cooking, the CON and SF pork loins contained 0.03 to 0.05 mg DHA/g of pork and the DHA injected loins contained approximately 1.46 mg DHA/g. This also changed the fatty acid profile of omega-6：omega-3 from, 5 to 1 in the CON pork, to a ratio of 1.7 to 1 in DHA pork. The appearance, odor, oxidation rates and sensory taste, as judged by a trained panel, determined the DHA injected meat to be, ＇slightly desirable＇ and gave lower ＇off flavour＇ scores, relative to the CON and SF injected pork. Pork can be fortified with DHA oil to 146 mg/100 g serving, which would meet half the recommended daily omega 3 fatty acid requirements for adult humans and would be desirable in taste.

Fatty Acid Composition and Digestive Enzyme Activities of Rainbow Trout in Response to Dietary Docosahexaenoic Acid(DHA)and Eicosapentaenoic Acid(EPA)During Salinity Acclimation

This physiological study aimed to evaluate the effects of dietary docosahexaenoic acid(DHA)and eicosapentaenoic acid(EPA)on the fatty acid composition and digestive enzyme activities of rainbow trout(Oncorhynchus mykiss)during salinity acclimation.Rainbow trout with an average initial weight of 90.61 g±9.25 g were fed diets with the quantities of DHA and EPA equaling to 0.54%,0.95%,1.40%and 1.79%(abbreviated as DE-0.54,DE-0.95,DE-1.40,and DE-1.79,respectively)for eight weeks,after which the gastric and intestinal fatty acids composition were analyzed.Subsequently,the fish underwent salinity acclimation.On days 1,4,7,and 14 after the freshwater was replaced by seawater and at the end of the 8-week period,gastric and intestinal digestive enzyme activities were determined.The results showed that the gastric and intestinal DHA and EPA contents of the fish were positively correlated to their dietary DHA and EPA levels.Low dietary DHA and EPA levels inhibited the protease activity of rainbow trout.Fish in the DE-0.54 group increased the lipase activity to enhance the utilization of lipids maybe due to the inadequate essential fatty acids for fish in this group.Hence,rainbow trout in the DE-0.54 group failed to maintain suitable activities of digestive enzymes after salinity acclimation.Therefore,a diet with minimum 0.95%DHA and EPA levels is necessary for rainbow trout during salinity acclimation.

Encapsulation of docosahexaenoic acid (DHA) using self-assembling food-derived proteins for efficient biological functions

Docosahexaenoic acid(DHA;22n-6)possesses multiple biological functions, including antioxidant activity and ameliorating hypertriglyceridemia. However, the application of DHA has been limited due to poor aqueous solubility and susceptible to oxidation. Here, ovalbumin(O), myosin(M), 7S soy globulin(S), and β-lactoglobulin(β), hydrolyzed by chymotrypsin, self-assembled into micelles, respectively. Adding incremental DHA to micelles caused endogenous fluorescence quenching of O, M, S, and β micelles, implying successful incorporation of DHA into hydrophobic cores of micelles(O(DHA), M(DHA), S(DHA), and β(DHA)). The results showed that micelles provided spatial stability and improved solubility, and stability against thermal and ultraviolet(UV)light for DHA. The uptake of DHA from M(DHA), β(DHA), O(DHA), and S(DHA)was 3.27-, 3.91-, 2.7-, and 3.95-fold higher, respectively, than that of DHA by Caco-2 cells. Encapsulation in micelles increased DHA aqueous solubility and uptake, which enhanced cellular endogenous antioxidant defense. Meanwhile, increased uptake of DHA was verified by HepG2 cells, and O, M, S, and β micelles were proven to increase DHA uptake to reduce lipid deposition. Our findings strongly support the possibility that O, M, S, and β micelles can be regarded as a carrier for loading DHA.

Identity and Safety of a Novel <i>Aurantiochytrium sp.</i>for Terrestrial Heterotrophic Docosahexaenoic Acid Production

The objective of the studies in this paper was to expand on the published toxicological assessment of Aurantiochytrium limacinum (AURA) with further strain characterization and to investigate the potential for the biomass or extracted oil to have antimicrobial properties or undesirable substances. AURA is being investigated as a novel source of the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) for enriching foods of animal origin by means of feed supplementation. In the first studies, we provided the 18S rRNA identification of the novel marine isolated thraustochytrid, established the nutritional composition of AURA biomass for application as a food or feed ingredient including proximate analysis and fatty acid profiling, and confirmed the DHA production potential of the strain. We determined through minimum inhibitory concentration (MIC) analysis that the unextracted AURA biomass was safe, showing no antimicrobial influence and no evidence of any deleterious effects of this product or its extracts at concentrations up to 1% w/w on the reference human intestinal bacteria tested. This would indicate that AURA should not stimulate selective pressure on the commensal microbiota and is therefore unlikely to aid development of antimicrobial resistance and the concomitant harm to humans and animals. Further analysis revealed that the AURA biomass produced through industrial heterotrophic fermentation was free from undesirables;toxic marine microalgal metabolites, heavy metals, pesticides, microbial contaminants, and mycotoxins. Including heterotrophically-grown AURA in food or feed, up to 1% w/w, is a safe and environmentally beneficial strategy for DHA supplementation.

Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide Aβ1-42 Reassures Its Therapeutic Utility

The accumulation of amyloid β peptide1-42 (Aβ1-42) masses in the brains of Alzheimer’s Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ1-42 curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ1-42 were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ1-42. Computational analyses of the binding of DHA to Aβ1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ1-42 fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.

Pilot trial evaluating maternal docosahexaenoic acid consumption during pregnancy: Decreased postpartum depressive symptomatology

Objective:Docosahexaenoic acid(DHA,22:6,n-3)is a major structural component of neural tissue critical to neurotransmission and mood regulation.Poor maternal dietary intake coupled with accelerated maternal-fetal transfer of DHA compound risk for maternal deficiency.The objective of this investigation was to determine if maternal DHA supplementation is efficacious in reducing symptoms of postpartum depression.Methods:This pilot investigation was a randomized,double-blinded,placebo controlled investigation of the role of DHA in preventing risk for postpartum depression.Women were assigned to:i)Placebo(no DHA,corn oil capsule),ii)DHA(300 mg DHA,fish oil capsule).Capsules were consumed from 24 to 40 weeks gestation(1 capsule 5 days/week).Forty-two participants were recruited(n=20,intervention;n=22,placebo).Maternal DHA status and depressive symptoms were followed from 24 to 40 weeks gestation using the Center for Epidemiologic Studies Depression Scale(CES-D)and the Postpartum Depression Screening Scale(PDSS)from 2 weeks to 6 months postpartum.Results:PDSS total scores were significantly lower(p=0.016;46.03±2.17,intervention vs.52.11±2.4,placebo)in the intervention group with less anxiety/insecurity(p=0.03),emotional lability(p=0.04)and loss of self(p=0.02).Conclusions:Women in the DHA intervention group had fewer symptoms of postpartum depression compared to the placebo group.These results support the notion that the consumption of DHA by pregnant women can be efficacious in preventing depressive symptoms and highlight a need for further larger-scale investigations using the PDSS in tandem with a diagnostic evaluation.

Visualization of decreased docosahexaenoic acid in the hippocampus of rats fed an n – 3 fatty acid-deficient diet by imaging mass spectrometry

The present study employed an imaging mass spectrometry (IMS) method to evaluate the effect of dietary n – 3 fatty acids on the fatty acid composition in rat brain. Rats were divided into two groups and fed either an n – 3 fatty acid-deficient or adequate diet. We determined the decreased n – 3 fatty acids in the hippocampus of rats fed an n – 3 fatty acid-deficient diet compared to the control. IMS visualization was achieved at a resolution of 100 m in rat brain, and showed decreased docosahexaenoic acid (DHA)-containing phosphatidyl choline (PC) or phosphatidyl ethanolamine (PE) in the hippocampus of rats fed an n – 3 fatty acid-deficient diet.

Docosahexaenoic Acid and Eicosapentaenoic Acid Modulate Calcium Signaling in Murine CD36-Positive Taste Buds Cells, via Phospholipase Pathways

DHA （docosahexaenoic acid） and EPA （eicosapentaenoic acid） induced intracellular calcium increase in taste receptor cells purified from mouse circumvallate papillae. We have demonstrated that DHA and EPA induced calcium increase respectively via cPLA2 （cytosolic phospholipase A2） type lVc and calcium independent iPLA2 （phospholipase A2） type VI. Intracellular calcium increases via PLC （phospholipase C） pathway and leads to a calcium effiux and further SOC （stored operated calcium） channels activation. An abundant increase in intracellular calcium will induce exocytosis of neurotransmitters into the extracellular medium. Our results suggest that DHA and EPA induced calcium signaling, and should be implicated in the transmission of lipid gustatory information to afferent nerve fibers, as shown previously with linoleic acid.