The effect of choline availability from gestation to early development on brain and retina functions and phospholipid composition in a male mouse model.

OBJECTIVES: Although choline is essential for brain development and neural function, the effect of choline on retina function is not well understood. This study examined the effects of choline on neural tissues of brain and retina, and membrane phospholipid (PL) composition during fetal development. METHODS: Pregnant C57BL/6 mice were fed one of 4 choline modified diets: i) control (Cont, 2.5g/kg), ii) choline deficient (Def, 0g/kg), iii) supplemented with choline chloride (Cho, 10g/kg) and iv) supplemented with egg phosphatidylcholine (PC, 10g/kg). At postnatal day (PD) 21, pups were weaned onto their mothers' respective diets until PD 45. Spatial memory was measured using the Morris Water Maze; retina function by electroretinogram (ERG); and PL composition with nuclear magnetic resonance spectroscopy. RESULTS: Cho and PC supplementation enhanced cued learning and spatial memory abilities, respectively (p Def > PC > Cho, with no statistically significant alterations in cone-driven responses. There were no differences in the composition of major PLs in the brain and retina. In the brain, subclasses of ether PL, alkyl acyl- phosphatidylethanolamine (PEaa) and phosphatidylcholine (PCaa) were significantly greater among the PC supplemented group in comparison to the Def group. DISCUSSION: These results indicate that while choline supplementation during gestation to an early developmental period is beneficial for spatial memory, contributions to retina function are minor. Assessment with a larger sample size of retinas could warrant the essentiality of choline for retina development.

Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia-reperfusion injury.

Myocardial ischemia-reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs), which results in cell death. However, the mechanism by which OxPCs mediate cell death and cardiac dysfunction is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Adult rat ventricular cardiomyocytes were treated with increasing concentrations of various purified fragmented OxPCs. Cardiomyocyte viability, bioenergetic response, and calcium transients were determined in the presence of OxPCs. Five different fragmented OxPCs resulted in a decrease in cell viability, with 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC) having the most potent cardiotoxic effect in both a concentration and time dependent manner (P < 0.05). POVPC and PONPC also caused a significant decrease in Ca2+ transients and net contraction in isolated cardiomyocytes compared to vehicle treated control cells (P < 0.05). PONPC depressed maximal respiration rate (P < 0.01; 54%) and spare respiratory capacity (P < 0.01; 54.5%). Notably, neither caspase 3 activation or TUNEL staining was observed in cells treated with either POVPC or PONPC. Further, cardiac myocytes treated with OxPCs were indistinguishable from vehicle-treated control cells with respect to nuclear high-mobility group box protein 1 (HMGBP1) activity. However, glutathione peroxidase 4 activity was markedly suppressed in cardiomyocytes treated with POVPC and PONPC coincident with increased ferroptosis. Importantly, cell death induced by OxPCs could be suppressed by E06 Ab, directed against OxPCs or by ferrostatin-1, which bound the sn-2 aldehyde of POVPC during I/R. The findings of the present study demonstrate that oxidation of phosphatidylcholines during I/R generate bioactive phospholipid intermediates that disrupt mitochondrial bioenergetics and calcium transients and provoke wide spread cell death through ferroptosis. Neutralization of OxPC with E06 or with ferrostatin-1 prevents cell death during reperfusion. Our study demonstrates a novel signaling pathway that operationally links generation of OxPC during cardiac I/R to ferroptosis. Interventions designed to target OxPCs may prove beneficial in mitigating ferroptosis during I/R injury in individuals with ischemic heart disease.NEW & NOTEWORTHY Oxidized phosphatidylcholines (OxPC) generated during reperfusion injury are potent inducers of cardiomyocyte death. Our studies have shown that OxPCs exert this effect through a ferroptotic process that can be attenuated. A better understanding of the OxPC cell death pathway can prove a novel strategy for prevention of cell death during myocardial reperfusion injury.

Differential effect of a carotenoid-rich diet on retina function in non-diabetic and diabetic rats.

Objective: This study was designed to examine the supplementation of a carotenoid-rich carrot powder, on retina function and carotenoid metabolism in non-diabetic control and type 1 diabetic animals. Methods: Male Wistar rats (n = 30) were randomly assigned to diets supplemented with (n = 15) or without (n = 15) carrot powder enriched diets (150 g/kg diet). After 3 weeks of diet adaptation, 8 rats in each group were treated with streptozotocin (iv) to induce type 1 diabetes and fed for a further 9 wk. Retinal function was assessed with the electroretinogram (ERG). Hepatic and plasma retinoids and carotenoids were measured by ultra-performance liquid chromatography. Results: Non-diabetic control rats fed the carrot diet had significantly (p < 0.02) higher rod- and cone- driven post-synaptic b-wave amplitudes, respectively, compared to those fed the control diet. These functional changes correlated with higher (p < 0.05) liver levels of carotenoids (α- and ß- carotene) and retinoids. In diabetic rats, carrot diet exacerbated retina dysfunction; the amplitudes for most of rod- and cone-driven ERG components were the lowest amplitudes among all groups (p < 0.02). Diabetic rats fed the carrot diet had lower hepatic retinol and retinyl palmitate, while having higher α- and ß-carotene levels, indicating diminished hepatic conversion of carotenoids into retinoids. Discussion: Dietary supplementation of high dose dietary carotenoids plays a beneficial role on healthy rat retina function, but exerts a detrimental effect in diabetes, which warrants undertaking detailed mechanistic studies.

Food Type and Lentil Variety Affect Satiety Responses but Not Food Intake in Healthy Adults When Lentils Are Substituted for Commonly Consumed Carbohydrates.

BACKGROUND: Lentils have potential to increase satiety and may contribute to a body weight management strategy; however, the effects on satiety of replacing common food ingredients with lentils within food products remain largely unknown. OBJECTIVE: The aim of this study was to determine the effects of replacing wheat and rice with 2 lentil varieties within muffins and chilies on satiety, test-meal food intake, and 24-h energy intake. METHODS: Healthy adults consumed muffins or chilies in which wheat or rice was substituted with green (61.8 g) or red (54 g) lentils in 2 randomized crossover studies (muffin study: n = 24, mean ± SE age: 25.4 ± 0.9 y, BMI (in kg/m2): 23.2 ± 0.5; chili study: n = 24, age: 25.7 ± 1.0 y, BMI: 23.2 ± 0.5), with ≥1-wk washout periods between study visits and studies. Subjective appetite sensations measured over 180 min were summarized with total area under the curve (AUC), food intake was measured at an ad libitum test meal, and 24-h energy intake was measured using weighed food records. Treatment effects were compared within each study using repeated-measures ANCOVA (subjective appetite sensations) and ANOVA (food intake, 24-h energy intake). RESULTS: Green, but not red, lentil chili significantly increased fullness AUC (17.5%, P = 0.02) and decreased desire to eat AUC (20.1%, P = 0.02) and prospective food consumption AUC (16.7%, P = 0.04) compared with rice chili, with no significant differences between chili treatments for test-meal food intake or 24-h energy intake. Muffin treatments did not significantly differ for any outcomes. CONCLUSIONS: Replacing rice with green, but not red lentils within chili increases satiety but does not decrease food intake, whereas replacing wheat with lentils within muffins does not increase satiety or decrease food intake in healthy adults. Further study of the role of lentil replacement in food products in body weight management is warranted. This trial was registered at clinicaltrials.gov as NCT03128684.

Effect of milled flaxseed and storage conditions on sensory properties and selected bioactive compounds in banana and cinnamon muffins used in a clinical trial.

BACKGROUND: Muffins containing 0, 20, and 30 g of flaxseed were developed for a randomized, controlled cross-over trial on low-density lipoprotein (LDL) cholesterol lowering. The effect of milled flaxseed and storage (-20 °C for 1 and 6 months) of banana and cinnamon muffins on sensory attribute intensities, selected physical properties, bioactive concentrations, and acceptability by two groups - clinical trial participants and consumers - was investigated. RESULTS: The addition of flax increased flax aroma and flavor, sour aroma, and cohesiveness of mass and brown color, and decreased sweet aroma and flavor, banana and cinnamon aroma and flavor, springiness and mouth dryness. Alpha-linolenic acid and secoisolariciresinol diglucoside were significantly increased when flax was increased from 20 to 30 g. Clinical trial participants generally found the muffins more acceptable than the consumers. Consumers reported significantly decreased acceptability when flax at any level was added to muffins, with 30 g the least acceptable. CONCLUSIONS: Muffins with 20 g flaxseed generally had higher mean acceptability values compared to muffins with 30 g. Neither flavoring nor storage at -20 °C for 6 months appreciably changed muffin attributes or acceptability. Future work will optimize the ingredients as well as the amount of flax needed to provide the required amount of bioactive to positively affect LDL cholesterol level and to produce acceptable muffins. © 2018 Society of Chemical Industry.

Investigation of low molecular weight peptides (<1 kDa) in chicken meat and their contribution to meat flavor formation.

BACKGROUND: Low molecular weight peptides (LMWPs) (<1 kDa) generated in meat during chilled conditioning can act as flavor precursors in the Maillard reaction with a potential contribution to key volatile organic compound (VOC) formation upon heating. Liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/QTOF-MS) successfully detected 44 LMWPs in chicken breast and thigh muscles stored at 4 °C for up to 6 days. Carnosine (350 mg per 100 g), glutathione (GSH, 20 mg per 100 g) (concentrations based on reported values in the literature) and cysteine glycine (Cys Gly, 5 mg per 100 g) (concentration based on results from LC/QTOF-MS) were used in model systems containing ribose (25 mg per 100 g). The three model systems were heated at 180 °C for 2 h at pH 6.3. VOCs were measured by simultaneous distillation solvent extraction/gas chromatography/mass spectrometry. RESULTS: Of 33 VOCs detected, 26 were significantly different (P ≤ 0.05) between the three peptides. The majority of nitrogen-containing volatiles, pyrazines and pyridines, dominated the carnosine mixture, while sulfur-containing VOCs dominated the GSH and Cys Gly peptide mixtures. CONCLUSION: Known key aroma compounds such as thiazole (meaty), 2-methyl-3-furanthiol (beef and meat), 2-furfurylthiol (roasted), dihydro-2-methyl-3(2H)-thiophenone (meaty), 2-acetylthiazole (meaty and roasted) and pyrazine (meaty) were detected under conditions specific to aged and thermally treated chicken, suggesting a potential contribution to the overall sensory quality of cooked meat. © 2018 Society of Chemical Industry.

Metabolomics and fetal alcohol spectrum disorder.

Fetal alcohol spectrum disorder (FASD) is a major public health issue that encompass an array of physical, neurological, and behavioral effects due to alcohol consumption during pregnancy. The classical biomarkers of FASD that are currently used lack sensitivity and specificity, and as such there is an opportunity through the use of novel metabolomics analysis to identify new biomarkers to identify those at risk for FASD, which could more effectively aid in early intervention. The focus of this minireview is to identify current work that is being done in the field of metabolomics in FASD in utero, and to highlight promising metabolites that could act as biomarkers in the future. We will conclude with suggestions for further research, as there is a large gap of knowledge in this particular area of metabolomics.

Factors affecting the ortho- and retronasal perception of flavors: A review.

Flavor perception is a highly individual sensation, and is impacted by a number of factors. Olfaction is a critical element in fully experiencing flavor. In this review, we explore the differences between orthonasal (sniff) versus retronasal (mouth) olfaction, and provide a comprehensive summary of recent publications in this arena. Here we explore the complexities of flavor perception, including the role that select flavors and media have on identification and localization. We also discuss some common neural imaging techniques used in this field, as odorants activate different neural responses in diverse areas of the brain, as well as the different stimulation patterns derived from perceiving food and nonfood related odorants. The information provided will be useful for sensory scientists and industry alike for the development of novel food and beverages that positively impact the consumer experience.

Identification of urinary metabolites with potential blood pressure-lowering effects in lentil-fed spontaneously hypertensive rats.

PURPOSE: Urine samples were obtained from a previously completed study that showed lentil consumption attenuates the increase in blood pressure that occurs over time in spontaneously hypertensive rats (SHRs). The objective of the present study was to compare the metabolite profile of the urine samples from control and lentil-fed SHR in relation to the compounds present in lentils but not in other pulses. METHODS: The urine samples were from 17-week-old, male SHR fed semi-purified diet prepared with powder (30 %, w/w) from cooked whole pulses or a pulse-free control diet (n = 8/group) for 4 weeks. Pulse powders, control diet and urine samples were extracted using acetonitrile and analyzed by a high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). RESULTS: Twenty-seven metabolites were significantly different in urine samples from lentil-fed SHR compared to SHR fed control diet, but only 7 were not present in the urine of SHR fed other pulses. Of these metabolites, only citrulline is linked to blood pressure regulation via production of the vasodilator nitric oxide (NO). Several arginine-related compounds that are NO synthase substrates or inhibitors were detected in lentils but not the control diet or other pulse powders. CONCLUSIONS: Consumption of lentils increases the availability of arginine and several related compounds that could potentially elevate production of NO and contribute to the blood pressure-lowering effects of lentil-rich diets.

A Vitamin B-6 Antagonist from Flaxseed Perturbs Amino Acid Metabolism in Moderately Vitamin B-6-Deficient Male Rats.

BACKGROUND: Pyridoxal 5'-phosphate (PLP) plays a crucial role as a cofactor in amino acid metabolism. There is a prevalence of moderate vitamin B-6 deficiency in the population that may be exacerbated through the ingestion of 1-amino d-proline (1ADP), a vitamin B-6 antagonist found in flaxseed. OBJECTIVE: Given prior evidence of the impact of synthetic 1ADP on indexes of pyridoxine metabolism, the current study was designed to investigate the effects of 1ADP derived from flaxseed on amino acid metabolism in moderately vitamin B-6-deficient rats. METHODS: Male weanling rats (n = 8/treatment) consumed a semipurified diet containing either 7 mg pyridoxine hydrochloride/kg diet [optimum vitamin B-6 (OB)] or 0.7 mg pyridoxine hydrochloride/kg diet [moderately vitamin B-6 deficient (MB)], each with 0 or 10 mg vitamin B-6 antagonist/kg diet, in either a synthetic form (1ADP) or as a flaxseed extract (FE), for 5 wk. At the end of the experiment, plasma vitamin B-6 and amino acid concentrations and the activities of hepatic PLP-dependent enzymes were analyzed. RESULTS: Compared with the MB control group, plasma PLP concentrations were 26% and 69% lower, respectively, in the MB+FE and MB+1ADP rats (P ≤ 0.001). In the MB+FE group, the plasma cystathionine concentration was 100% greater and the plasma α-aminobutyric acid and glutamic acid concentrations were 59% and 30% lower, respectively, than in the MB control group. Both synthetic 1ADP and FE significantly (P < 0.001) inhibited the in vitro hepatic activities of 2 PLP-dependent enzymes, cystathionine ß-synthase (up to 44%) and cystathionine γ-lyase (up to 60%), irrespective of vitamin B-6 concentrations. Because of vitamin B-6 antagonist exposure, observed perturbations in plasma biomarkers and hepatic enzyme activities were not evident or of lesser magnitude in rats consuming adequate vitamin B-6. CONCLUSION: The current data from a rat model provide evidence that a vitamin B-6 antagonist now prevalent in the human food supply may pose challenges to individuals of moderate vitamin B-6 status.

Investigation of vitamin B6 inadequacy, induced by exposure to the anti-B6 factor 1-amino D-proline, on plasma lipophilic metabolites of rats: a metabolomics approach.

PURPOSE: Vitamin B6 status in the body is affected by several factors including dietary supply of the antivitamin B6 factor, 1-amino D-proline (1ADP), which is present in flaxseed. Owing to the prevalence of moderate B6 deficiency in the general population, a co-occurrence of 1ADP may lead to a further deterioration of B6 status. To this end, we applied a nontargeted metabolomics approach to identify potential plasma lipophilic biomarkers of deleterious effect of 1ADP on moderately vitamin B6-deficient rats using a high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. METHODS: Twenty-four rats were fed with a semi-purified diet containing pyridoxine·HCl (PN·HCl) either 7 mg/kg diet (optimal B6) or 0.7 mg/kg diet (moderate B6). The rats were divided into four treatments (n = 6), and one treatment in each B6 diet group was also fed ad libitum with 10 mg/kg diet of synthetic 1ADP. After 5 weeks of study, plasma was collected from the rats and lipophilic metabolites were extracted using acetonitrile as a solvent for analysis. RESULTS: Ten potential plasma lipophilic biomarkers were identified out of >2500 detected entities, which showed significant differences between the treatments. Plasma glycocholic acid, glycoursodeoxycholic acid, murocholic acid, N-docosahexaenoyl GABA, N-arachidonoyl GABA, lumula, nandrolone and orthothymotinic acid concentrations were significantly elevated, while plasma cystamine and 3-methyleneoxindole concentrations were significantly reduced as a result of either low B6 status or 1ADP or their interaction. CONCLUSION: Changes in these metabolites revealed a potential defect in pathways linked with the biosynthesis and metabolism of bile acid components, N-acyl amino acids, analgesic androgens, anti-inflammatory and neuroprotective molecules. We also noted that the changes in these biomarkers can be alleviated by the application of adequate vitamin B6.

The effect of flaxseed dose on circulating concentrations of alpha-linolenic acid and secoisolariciresinol diglucoside derived enterolignans in young, healthy adults.

PURPOSE: The primary endpoint was to determine the plasma concentration of alpha-linolenic acid (ALA), and its metabolites, following milled flaxseed consumption at four doses. Secondary outcomes focused on plasma enterolignan concentrations and the effects on tolerability, platelet aggregation, plasma lipids and urinary thromboxane levels. METHODS: Healthy, younger adults (n = 34; 18-49 years old) were randomized into four groups consuming one muffin daily for 30 days fortified with 10, 20, 30 or 40 g of milled flaxseed. Blood and urine were collected at baseline and 4 weeks. RESULTS: Plasma ALA concentrations increased with all flaxseed doses (P < 0.01), except the 20 g/day dose (P = 0.10), yet there was no significant dose-dependent response (P = 0.81). Only with the 30 g/day diet were n-3 polyunsaturated fatty acids (P = 0.007), and eicosapentaenoic acid (EPA) (P = 0.047) increased from baseline values. Docosapentaenoic acid and docosahexaenoic acid were not detected at any dose. Plasma total enterolignan concentrations significantly increased over time in all treatment groups, yet despite a dose-dependent tendency, no between-group differences were detected (P = 0.22). Flaxseed was well tolerated, even at the highest dose, as there were no reported adverse events, changes in cholesterol, platelet aggregation or urinary 11-dehydro-thromboxane B2. CONCLUSIONS: In healthy, younger adults, 10 g/day of milled flaxseed consumption is sufficient to significantly increase circulating ALA and total enterolignan concentrations; however, 30 g/day is required to convert ALA to EPA. Although all doses were well tolerated, 40 g/day is too low to attenuate cholesterol in this population.

Maternal obesity characterized by gestational diabetes increases the susceptibility of rat offspring to hepatic steatosis via a disrupted liver metabolome.

Maternal obesity is associated with a high risk for gestational diabetes mellitus (GDM), which is a common complication of pregnancy. The influence of maternal obesity and GDM on the metabolic health of the offspring is poorly understood. We hypothesize that GDM associated with maternal obesity will cause obesity, insulin resistance and hepatic steatosis in the offspring. Female Sprague-Dawley rats were fed a high-fat (45%) and sucrose (HFS) diet to cause maternal obesity and GDM. Lean control pregnant rats received low-fat (LF; 10%) diets. To investigate the interaction between the prenatal environment and postnatal diets, rat offspring were assigned to LF or HFS diets for 12 weeks, and insulin sensitivity and hepatic steatosis were evaluated. Pregnant GDM dams exhibited excessive gestational weight gain, hyperinsulinaemia and hyperglycaemia. Offspring of GDM dams gained more weight than the offspring of lean dams due to excess adiposity. The offspring of GDM dams also developed hepatic steatosis and insulin resistance. The postnatal consumption of a LF diet did not protect offspring of GDM dams against these metabolic disorders. Analysis of the hepatic metabolome revealed increased diacylglycerol and reduced phosphatidylethanolamine in the offspring of GDM dams compared to offspring of lean dams. Consistent with altered lipid metabolism, the expression of CTP:phosphoethanolamine cytidylyltransferase, and peroxisomal proliferator activated receptor-α mRNA was reduced in the livers of GDM offspring. GDM exposure programs gene expression and hepatic metabolite levels and drives the development of hepatic steatosis and insulin resistance in young adult rat offspring.

Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease.

BACKGROUND: Dietary flaxseed lowers cholesterol in healthy subjects with mild biomarkers of cardiovascular disease (CVD). OBJECTIVE: The aim was to investigate the effects of dietary flaxseed on plasma cholesterol in a patient population with clinically significant CVD and in those administered cholesterol-lowering medications (CLMs), primarily statins. METHODS: This double-blind, randomized, placebo-controlled trial examined the effects of a diet supplemented for 12 mo with foods that contained either 30 g of milled flaxseed [milled flaxseed treatment (FX) group; n = 58] or 30 g of whole wheat [placebo (PL) group; n = 52] in a patient population with peripheral artery disease (PAD). Plasma lipids were measured at 0, 1, 6, and 12 mo. RESULTS: Dietary flaxseed in PAD patients resulted in a 15% reduction in circulating LDL cholesterol as early as 1 mo into the trial (P = 0.05). The concentration in the FX group (2.1 ± 0.10 mmol/L) tended to be less than in the PL group (2.5 ± 0.2 mmol/L) at 6 mo (P = 0.12), but not at 12 mo (P = 0.33). Total cholesterol also tended to be lower in the FX group than in the PL group at 1 mo (11%, P = 0.05) and 6 mo (11%, P = 0.07), but not at 12 mo (P = 0.24). In a subgroup of patients taking flaxseed and CLM (n = 36), LDL-cholesterol concentrations were lowered by 8.5% ± 3.0% compared with baseline after 12 mo. This differed from the PL + CLM subgroup (n = 26), which increased by 3.0% ± 4.4% (P = 0.030) to a final concentration of 2.2 ± 0.1 mmol/L. CONCLUSIONS: Milled flaxseed lowers total and LDL cholesterol in patients with PAD and has additional LDL-cholesterol-lowering capabilities when used in conjunction with CLMs. This trial was registered at clinicaltrials.gov as NCT00781950.

Flaxseed for hypertension: implications for blood pressure regulation.

Hypertension is the single largest risk factor attributed to mortality in the world. Medications are the primary treatment for hypertension; however, adherence to drug regimens is low (~50 %). Low adherence may be a contributing factor leading to uncontrolled blood pressure in patients. An effective alternative or complement to medications in managing hypertension is through lifestyle modifications. Adopting a healthy diet is a valuable strategy. A recent, randomized controlled year-long trial observed impressive reductions in blood pressure in patients with hypertension consuming flaxseed daily. Therefore, attention has been garnered for flaxseed as a potentially valuable strategy for the management of hypertension. This review will highlight the recent data for flaxseed and its extracts in blood pressure regulation in both animal models and clinical trials. Insight into the proposed anti-hypertensive mechanism of flaxseed and the implications of flaxseed as a potential global anti-hypertensive therapy will be discussed.

Zinc deficiency and taste perception in the elderly.

Taste, one of the major senses in humans, is the ability to detect the flavor of substances such as food, certain minerals, and poisons. Taste distortions in human beings have been attributed to various physiological and environmental factors including aging and disease conditions. Given the fact that taste is one of the most important factors in food preference, selection, and consumption, the decreased appetite in the elderly, probably due to disease conditions, may lead to dietary restrictions that could negatively impact nutritional and health status. The role of zinc on taste distortion in the elderly population and taste impairment are described. Although several studies demonstrate the associative nature of taste degeneration with age, additional investigations are required to clarify the mechanisms by which taste perception is altered with age.

Aroma and taste perceptions with Alzheimer disease and stroke.

Chemosensory disorders of smell or taste in humans have been attributed to various physiological and environmental factors including aging and disease conditions. Aroma and taste greatly condition our food preference, selection and, consumption; the decreased appetite in patients with known neurodegenerative diseases may lead to dietary restrictions that could negatively impact nutritional and health status. The decline in olfactory and gustatory systems in patients with Alzheimer disease and various types of stroke are described.

Lipidomic Predictors of Coronary No-Reflow.

The 'no-reflow' phenomenon (NRP) after primary percutaneous coronary intervention (PCI) is a serious complication among acute ST-segment elevation myocardial infarction (STEMI) patients. Herein, a comprehensive lipidomics approach was used to quantify over 300 distinct molecular species in circulating plasma from 126 patients with STEMI before and after primary PCI. Our analysis showed that three lipid classes: phosphatidylcholine (PC), alkylphosphatidylcholine (PC(O)), and sphingomyelin (SM), were significantly elevated (p < 0.05) in no-reflow patients before primary PCI. The levels of individual fatty acids and total fatty acid levels were significantly lower (p < 0.05) in no-reflow subjects after PCI. The grouping of patients based on ECG ST-segment resolution (STR) also demonstrated the same trend, confirming the possible role of these differential lipids in the setting of no-reflow. Sphingomyelin species, SM 41:1 and SM 41:2, was invariably positively correlated with corrected TIMI frame count (CTFC) at pre-PCI and post-PCI. The plasma levels of SM 42:1 exhibited an inverse association (p < 0.05) consistently with tumor necrosis factor-alpha (TNF-α) at pre-PCI and post-PCI. In conclusion, we identified plasma lipid profiles that distinguish individuals at risk of no-reflow and provided novel insights into how dyslipidemia may contribute to NRP after primary PCI.

CRISPR/Cas9-mediated lipoxygenase gene-editing in yellow pea leads to major changes in fatty acid and flavor profiles.

Introduction: Although pulses are nutritious foods containing high amounts of protein, fiber and phytochemicals, their consumption and use in the food industry have been limited due to the formation of unappealing flavors/aromas described as beany, green, and grassy. Lipoxygenase (LOX) enzymes are prevalent among pulse seeds, and their activity can lead to the formation of specific volatile organic compounds (VOCs) from certain polyunsaturated fatty acids (PUFAs). As a widespread issue in legumes, including soybean, these VOCs have been linked to certain unappealing taste perception of foods containing processed pulse seeds. Methods: To address this problem in pea and as proof of principle to promote the wider use of pulses, a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) construct was designed to create null alleles (knockouts) of PsLOX2 which had been implicated in the generation of VOCs in peas. Results and discussion: Successful CRISPR/Cas9-mediated LOX gene editing of stable transgenic pea lines (TGP) was confirmed by DNA sequencing of the wild type (WT) and TGP pslox2 mutant lines. These lines were also assessed for LOX activity, PUFA levels, and VOCs. Compared to WT peas, the TGP lines showed a significant reduction (p < 0.05) in LOX activity and in the concentration of key VOCs, including hexanal, 2-hexenal, heptanal, (E)-2-heptenal, (E,E)-2,4-heptadienal, 1-octen-3-ol, octanal, (E)-2-octenal (E,E)-2,4-nonadienal and furan-2-pentyl. The content of two essential PUFAs, linoleic and α-linolenic acids, the known substrates of LOX in plants, was higher in TGP flours, indicating the efficacy of the CRISPR-mediated gene editing in minimizing their oxidation and the further modification of PUFAs and their products. The collection of VOCs from the headspace of ground pea seeds, using a portable eNose also distinguished the TGP and WT lines. Multiple regression analysis showed that LOX activity correlated with the two VOCs, heptanal and (E,E)-2,4-heptadienal in pea flours. Partial Least Squares Regression (PLS-R) plot for selected PUFAs, VOCs, and sensor responses in WT and TGP lines showed distinct clusters for WT and TGP lines. Together this data demonstrates the utility of CRISPR mediated mutagenesis of PsLOX2 to quickly improve aroma and fatty acid (FA) profiles of pea seeds of an elite Canadian variety.

Patterns of alpha-linolenic acid incorporation into phospholipids in H4IIE cells.

Alpha linolenic acid (ALA) is an 18-carbon essential fatty acid found in plant-based foods and oils. While much attention has been placed on conversion of ALA to long chain polyunsaturated fatty acids, alternative routes of ALA metabolism exist and may lead to formation of other bioactive metabolites of ALA. The current study employed a non-targeted metabolomics approach to profile ALA metabolites that are significantly upregulated by ALA treatment. H4IIE hepatoma cells (n=3 samples per time point) were treated with 60 µM ALA or vehicle for 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 h. Samples were then extracted with methanol and analyzed using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. We observed selective changes in ALA incorporation into phospholipid classes and subclasses over the 12 h following ALA treatment. While levels of specific molecular species of ALA-containing phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and lysophospholipids were elevated with ALA treatment, others were not affected. Of the phospholipids that were increased, some (e.g., PC[18:3/18:1], PC[18:3/18:4], PE[18:3/18:2], PE[18:3/18:3]) were elevated almost immediately after exposure to ALA, while others [e.g., PE[18:1/18:3] PA[18:3/22:6], and PA[18:3/18:2]) were not elevated until several hours after ALA treatment. Overall, these results suggest that ALA incorporation into phospholipids is selective and support a metabolic hierarchy for ALA incorporation into specific phospholipids. Given the functionality of phospholipids based on their fatty acid composition, future studies will need to investigate the implications of ALA incorporation into specific phospholipids on cell function.