Unusual polyunsaturated fatty acids in edible marine worms identified by covalent adduct chemical ionization mass spectrometry.

Non-traditional seafood, such as spoon worms (Urechis unicinctus) and peanut worms (Sipunculus nudus), serves as both delicacies and potential solutions to the global food insecurity crisis. Despite being consumed primarily in parts of China, Korea, and Japan, the nutritional values especially the complex fatty acid compositions of these marine worms are difficult to characterize. To overcome this obstacle, we employed covalent adduct chemical ionization (CACI) tandem mass spectrometry for the de novo identification of their unusual polyunsaturated fatty acids (PUFA). Through this method, we identified several PUFA with polymethylene-interrupted (PMI) double bond configurations, including 22:3(7Z,13Z,16Z), a novel PUFA derived from sciadonic acid. U. unicinctus exhibits an exceptionally low n-6/n-3 PUFA ratio of 0.15, making it a potential functional food to counterbalance the n-6/n-3 imbalance in modern diets. S. nudus boasts notably high concentrations (∼3 %, wt/wt) of branched chain fatty acids (BCFA), exceeding typical levels found in dairy products.

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.

Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

Overcoming biological barriers BBB/BBTB by designing PUFA functionalised lipid-based nanocarriers for glioblastoma targeted therapy.

A major obstacle for chemotherapeutics in Glioblastoma (GB) is to reach the tumour cells due to the presence of the blood-brain barrier (BBB) and chemoresistance of anticancer drugs. The present study reports two polyunsaturated fatty acids, gamma-linolenic acid (GLA) and alpha-linolenic acid (ALA) appended nanostructured lipid carriers (NLCs) of a CNS negative chemotherapeutic drug docetaxel (DTX) for targeted delivery to GB. The ligand appended DTX-NLCs demonstrated particle size < 160 nm, PDI < 0.29 and a negative surface charge. The successful linkage of GLA (41 %) and ALA (30 %) ligand conjugation to DTX- NLCs was confirmed by diminished surface amino groups on the NLCs, lower surface charge and FTIR profiling. Fluorophore labelled GLA-DTX-NLCs and ALA-DTX-NLCs permeated the in-vitro 3D BBB model with Papp values of 1.8 × 10-3 and 1.9 × 10-3 cm/s respectively. Following permeation, both formulations showed enhanced uptake by GB immortalised cells while ALA-DTX-NLCs showed higher uptake in patient-derived GB cells as evidenced in an in-vitro 3D blood brain tumour barrier (BBTB) model. Both surface functionalised formulations showed higher internalisation in GB cells as compared to bare DTX-NLCs. ALA-DTX-NLCs and GLA-DTX-NLCs showed 13.9-fold and 6.8-fold higher DTX activity respectively at 24 h as indicated by IC50 values when tested in patient-derived GB cells. ALA-DTX-NLCs displayed better efficacy than GLA-DTX-NLCs when tested against 3D tumour spheroids and patient-derived cells. These novel formulations will contribute widely to overcoming biological barriers for treating glioblastoma.

Evaluation of Post-Larval Diets for Indoor Weaned Largemouth Bass (Micropterus salmoides).

This study aimed to evaluate different commercial diets (Otohime C1, Aller Futura (AF), Biomar Inicio Plus (BIP)) and one experimental feed (EF) in terms of their effectiveness as post-larval diets for indoor weaned largemouth bass, LMB (Micropterus salmoides). Key variations in the content of nutritive values were monounsaturated fatty acid (MUFA) and highly unsaturated FA (HUFA) ω3. Fish were fed with one of four tested diets from the 33rd to the 40th day post-hatch (DPH). Biometric indices, digestive enzyme-specific activities, thyroid hormone status, and mRNA expression of genes coding for skeleton, neuron, and muscle growth were analyzed. The lowest skeletal deformity rate and highest survival among the treatments were seen in BIP-fed fish. Dietary lipids, with an appropriate balance between MUFA and polyunsaturated FA (PUFA), alongside amino acid balance, were shown to be the main contributors to the growth of the skeleton and/or fish survival. On the other hand, fish growth is correlated with fish digestive capacity and feed moisture percent rather than feed quality. Unexpectedly, BIP-fed fish were attributed with the lowest expression of skeleton differentiation markers, which may reflect the sacrifice of scale and/or cranium growth at the expense of somatic growth. This study highlights the role of non-marine ingredients in the nutrition of post-larval LMB.

Exogenous tetracosahexaenoic acid modifies the fatty acid composition of human primary T lymphocytes and Jurkat T cell leukemia cells contingent on cell type.

Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with 24:6ω-3 on the fatty acid composition of two related cell types, primary CD3+ T lymphocytes and Jurkat T cell leukemia, which differ in the integrity of the polyunsaturated fatty acid (PUFA) biosynthesis pathway. 24:6ω-3 was only detected in either cell type when cells were incubated with 24:6ω-3. Incubation with 24:6ω-3 induced similar increments in the amount of 22:6ω-3 in both cell types and modified the homeoviscous adaptations fatty acid composition induced by activation of T lymphocytes. The effect of incubation with 18:3ω-3 compared to 24:6ω-3 on the increment in 22:6ω-3 was tested in Jurkat cells because primary T cells cannot convert 18:3ω-3 to 22:6ω-3. The increment in the 22:6ω-3 content of Jurkat cells incubated with 24:6ω-3 was 19.5-fold greater than that of cells incubated with 18:3ω-3. Acyl-coA oxidase siRNA knockdown decreased the amount of 22:6ω-3 and increased the amount of 24:6ω-3 in Jurkat cells. These findings show exogenous 24:6ω-3 can be incorporated into primary human T lymphocytes and Jurkat cells and induces changes in fatty acid composition consistent with its conversion to 22:6ω-3 via a mechanism involving peroxisomal ß-oxidation that is regulated independently from the integrity of the upstream PUFA synthesis pathway. One further implication is that consuming 24:6ω-3 may be an effective alternative means of achieving health benefits attributed to 20:5ω-3 and 22:6ω-3.

Association between polyunsaturated fatty acids intake and insulin resistance in Brazilian adolescents (ERICA Study).

OBJECTIVE: Some studies have proposed a beneficial effect of polyunsaturated fatty acid (PUFA) intake with regard to insulin sensitivity. The aim of this study was to estimate the energy percentage and the daily PUFA intake to investigate the association between PUFAs and insulin resistance in a large sample of Brazilian adolescents. METHODS: We evaluated 37 023 adolescents ages 12 to 17 y, who were participants in ERICA (Study of Cardiovascular Risk in Adolescents). Energy percentage and PUFA daily intake were extracted from a 24-h dietary recall. The mean daily intake of total fat, median, and the respective 95% confidence intervals (95% CI) of daily intake of linoleic acid (LA), α-linolenic acid (ALA) and the ratio of LA to ALA were estimated according to sociodemographic variables. Associations of PUFA and markers of glucose homeostasis were analyzed by Poisson regression model. RESULTS: Mean total fat intake was 30.1% of energy (95% CI, 29.9-30.4). Most participants met the current recommended values of PUFA and LA/ALA ratio ranging from 5:1 to 10:1 (80.9%, 95% CI, 79.8-81.8). ALA intake was inversely associated with higher waist circumference (prevalence ratio [PR], 0.996; 95% CI, 0.994-0.998). LA/ALA ratio ≥9:1 was significantly associated with higher levels of homeostasis model assessment of insulin resistance (HOMA-IR; PR, 1.01; 95% CI, 1.006-1.02), and ratio >10:1 also showed significant association with higher levels of HOMA-IR (PR, 1.02; 95% CI, 1.01-1.03) and glycated hemoglobin (PR, 1.14; 95% CI, 1.04-1.26). These associations remained significant after adjustment. CONCLUSION: Promotion of ALA intake and balanced LA/ALA ratio should be considered as a possible health strategy aimed at contributing to better control of glucose homeostasis and insulin resistance in adolescents.

Evaluation of biochemical composition of hulled and hull-less genotypes of pumpkin seeds grown in subtropical India.

Pumpkin seeds are one of the functional foods with most potential having myriad of uses, and functioning as both edible seeds and oilseeds. Nevertheless, their utilization is restricted to the presence of a thick seed coat (hull) which subjects them to the process of decortication, increasing the farmers' expense as well as limiting their utilization as oilseeds. Therefore, in the present study, characterization of the biochemical composition of the hulled (Punjab Chappan Kadoo-1 abbreviated as PCK-1) and hull-less (PAU Magaz Kadoo-1 abbreviated as PMK-1) genotype of pumpkin seeds was undertaken to assess the nutritional differences and their efficient application; PMK-1 is a new cultivar of pumpkin released by Punjab Agricultural University in 2018. Based on the characterization, the hulled genotype of pumpkin seeds was observed to possess higher content of total soluble proteins (79.62 mg/100 g), total free amino acids (3.48 g/100 g), moisture (6.74%), fibre content (21.1 g/100 g), antioxidant potential (26.15%), polyamines (19.2 mg/100 g), sterols (387.1 mg/100 g), and specific enzymatic activity whereas the hull-less genotype was observed to possess a higher amount of minerals (4.57 g/100 g), tocopherols (15.76 mg/100 g), and oil content (36%) respectively; most of the biochemical parameters do not differ from each other at a greater fold difference except for total free amino acids and fibre, which are nearly four times and three times higher in hulled seeds in comparison to the naked seeds respectively. The two genotypes of seeds do not compete, rather do complement each other in biochemical and nutritional composition.

Causal effects of fatty acids on depression: Mendelian randomization study.

Objectives: Fatty acids (FA) are widely believed to play a role in the pathophysiology of depression. However, the causal relationships between FA and depression remain elusive and warrant further research. We aimed to investigate the potential causal relationship between FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] and the risk of depression using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis using large-scale European-based genome-wide association studies (GWASs) summary data related to depression (n = 500,199 individuals) and FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] levels. MR analysis was performed using the Wald ratio and inverse variance-weighted (IVW) methods, and sensitivity analysis was conducted by the simple mode, weighted mode, weighted median method, and MR-Egger method. Results: We found the causal effects for the levels of oleic acid (OA; OR = 1.07, p = 5.72 × 10-4), adrenic acid (OR = 0.74, p = 1.01 × 10-3), α-linolenic acid (ALA; OR = 2.52, p = 1.01 × 10-3), eicosapentaenoic acid (EPA; OR = 0.84, p = 3.11 × 10-3) on depression risk, after Bonferroni correction. The sensitivity analyses indicated similar trends. No causal effect between the levels of SFA and depression risk was observed. Conclusion: Our study suggests that adrenic acid and EPA are protective against the risk of depression, while OA and ALA are potential risk factors for depression. Nonetheless, the underlying mechanisms that mediate the association between these FAs and depression risk should be investigated in further experiments.

Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice.

Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids.

Intakes of PUFA are low in preschool-aged children in the Guelph Family Health Study pilot cohort.

This study investigated intakes of total, n-3, and n-6 polyunsaturated fatty acids (PUFA) in 109 preschool-aged children who participated in the Guelph Family Health Study pilot. Intakes of total, n-3, and n-6 PUFA did not meet recommendations. This study highlights the need for additional monitoring and potential interventions to improve PUFA intake in preschool-aged children. Clinical Trial #NCT02223234. Novelty: Canadian preschool-aged children are not consuming enough n-3 and n-6 PUFA.

Plasma and red blood cell n3 fatty acids correlate positively with the WISC-R verbal and full-scale intelligence quotients and inversely with Conner's parent-rated ADHD index t-scores in children with high functioning autism and Asperger's syndrome.

Findings of the fatty acid status of people with autism spectrum disorders have been incongruent perhaps because of the diversity of the condition. A cross-sectional design study was used to  investigated fatty acid levels and relationships between fatty acids, and cognition and behaviour in a homogenous group of children with autism spectrum disorder. Children with Asperger's syndrome (AS) /high functioning autism (n = 44) and healthy siblings (n = 17) were recruited from the Diagnostic and Therapeutic Centre for Children with Autism, Warsaw, Poland. In the AS group, plasma phosphatidylcholine 22:5n3 correlated positively with verbal (r = 0.357, p = 0.019) and full scale (r = 0.402, p = 0.008) IQs, red blood cell phosphatidylcholine 22:5n3 with verbal (r = 0.308, p = 0.044), performance (r = 0.304, p = 0.047) and full scale (r = 0.388, p = 0.011) IQs and red blood cell phosphatidylethanolamine 22:5n3 with verbal (r = 0.390, p = 0.010) and full scale (r = 0.370, p = 0.016) IQs. Whilst, plasma phosphatidycholine 20:5n3 (r = -0.395, p = 0.009), 22:6n3 (r = -0.402, p = 0.007) and total n3 fatty acids (r = -425, p = 0.005), red blood cell phosphatidlycholine 20:5n3 (r = -0.321, p = 0.036) and red blood cell phosphatidylethanolamine 20:5n3 (r = -0.317, p = 0.038), 22:6n3 (r = -0.297, p = 0.05) and total n3 fatty acids (r = -0.306, p = 0.046) correlated inversly with ADHD index. Similarly, inattention was negatively related with plasma phosphatidylcholine 22:6n3 (r = -0.335, p = 0.028), and total n3 fatty acids (r = -0.340, p = 0.026), oppositional with plasma phosphatidylcholine 18:3n3 (r = -0.333, p = 0.029), 20:5n3 (r = -0.365, p = 0.016), total n3 fatty acids (r = -0.293, p < 0.05), red blood cell phosphatidylcholine 18:3n3 (r = -0.337, p = 0.027) and red blood cell ethanolamine 18:3n3 (r = - 0.333, p = 0.029), 20:5n3 (r = -0.328, p = 0.032), 22:6n3 (r = 0.362, p = 0.017) and total n-3 fatty acids (r = -0.298, p < 0.05) and hyperactivity with plasma phosphatidylcholine 22:6n3 (r = -0.320, p = 0.039). In contrast, there were inverse correlations between red blood cell phosphatidylcholine 18:2n6 and performance (r = -0.358, p = 0.019) and full scale (r = -0.320, p = 0.039) IQs, and direct correlations between red blood cell phosphatidylcholine 22:4n6 (r = 0.339, p = 0.026) and 22:5n6 (r = 0.298, p < 0.05) and ADHD index, between red blood cell phosphatidylcholine 22:4n6 (r = 0.308, p = 0.044) and inattention, between plasma phosphatidylcholine 22:4n6 (r = 0.341, p = 0.025), red blood cell phosphatidylcholine 20:4n6 (r = 0.314, p = 0.041) and total n6 fatty acids (r = 0.336, p = 0.028) and oppositional and plasma phosphatidylcholine 20:3n6 (r = 0.362, p = 0.018) and red blood cell phosphatidylcholine 20:3n6 (r = 0.401, p = 0.009) and hyperactivity. The findings of the ethnically homogenous children with Asperger's syndrome/high functioning autism study revealed positive associations between 22:5n3 and cognition, and negative relationships between 20:5n3 and 22:6n3 and behavioural problem. In contrast, cognitive ability and behavioural problems were negatively and positively associated with n6 fatty acids. Further investigation is required to establish whether there a cause and effect relationship. Regardless, it would be prudent to ensure that children with the conditions have optimum n3 PUFA intake.

Whole blood fatty acid profile of young subjects and adherence to the Mediterranean diet: an observational cohort study.

BACKGROUND: Relatively little is known about the physiological whole blood fatty acid composition in young people. Likewise, few studies have addressed the question of correlations between Mediterranean diet (MedDiet) adherence and blood fatty acids in childhood. METHODS: The fatty acid profile in whole blood from subjects, 46 days-19 years old (n = 152), without acute, chronic, or inflammatory diseases was analysed by gas chromatography. Dietary data was extracted from a 24-h recall in a subgroup of subjects (n = 60) into a modified Diet Quality Index for Children (KIDMED) questionnaire to evaluate MedDiet adherence. The cohort was divided into three age groups: < 2, 2- < 10, and 10-19 years. Kruskal-Wallis test and Bonferroni post hoc test were used to check for age group fatty acid differences. For correlations, Spearman's correlation coefficient and partial Spearman's correlation coefficient were used. RESULTS: Linoleic acid, EPA, DHA, palmitic acid, and total saturated fatty acids were stable over age groups. Dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), total polyunsaturated FAs (PUFA), and total omega-6 PUFA increased from age group < 2 years; alpha-linolenic acid, total omega-3 PUFA, oleic acid, and total monounsaturated FAs decreased. Adherence to the MedDiet was at low-medium level in 91.7% of the subjects. In the age group 2- < 10 yrs., the degree of adherence correlated positively with total MUFA and PUFA balance, negatively with total PUFA, total n6-PUFA, AA/DHA, AA/EPA, and n6/n3. Age did not influence the correlations as to PUFA balance and AA/EPA. CONCLUSIONS: Increased FA proportions with age were seen in the n6-series of PUFA. The n3-FA species decreased or were stable. The vast majority of the subjects with dietary data, 92%, obtained a KIDMED score indicative of low-medium adherence to the MedDiet. The score correlated negatively with various n6-species, i.e. the MedDiet suppressed circulating n6-PUFA. Whole blood may be used to investigate FAs and MedDiet adherence correlations which may be applied in the study of health issues in childhood.

African American Women with Cardiometabolic Complications of Pregnancy Have Decreased Serum Abundance of Specialized Pro-Resolving Lipid Mediators and Endocannabinoids.

African American (AA) women experience higher rates of maternal morbidity and mortality compared to US women of other racial/ ethnic groups. Cardiometabolic complications of pregnancy (including gestational diabetes, gestational hypertension, and preeclampsia) are leading contributors to maternal morbidity and mortality. Marked changes in circulating lipids are known to accompany cardiometabolic complications of pregnancy. Serum concentrations of docosahexaenoic acid (DHA) have been shown to be inversely correlated with risk for preeclampsia. DHA is a biosynthetic precursor of a class of specialized pro-resolving mediators (SPMs), resolvins, that have anti-inflammatory properties and are also associated with hypertensive disorders of pregnancy. We employed targeted lipidomics to characterize the distribution of DHA-containing phospholipids and SPMs in maternal serum collected in early and late pregnancy (8-14 weeks and 24-30 weeks gestation, respectively) to identify key lipids that are dysregulated during pregnancy in AA women who develop cardiometabolic complications. We identified a lipid signature in early pregnancy serum samples of AA women that is predictive of cardiometabolic complications of pregnancy with 74% accuracy. These are Resolvin D1, Resolvin E1, 2-AG, PGE2-glyerol ester, and 36:6 PC. These findings suggest that there are blood-based markers detectable in early pregnancy that can potentially identify persons at risk and tailor clinical interventions.

Effect of n-3 (Omega-3) Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers and Body Weight in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of RCTs.

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (-0.36 (-0.71 to -0.01)), glycated hemoglobulin (HbA1c) (-0.74 (-1.13 to -0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (-0.58 (-1.13 to -0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (-0.27 (-0.37 to -0.18)), total cholesterol (-0.60 (-0.88 to -0.32)), low density lipoprotein (LDL) (-0.54 (-0.85 to -0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker's tumor necrosis factor-alpha (TNF-α) (-0.13 (-0.75 to 0.48)) and c-reactive protein (CRP) (-0.72 (-1.70 to 0.27)), as well as weight (-0.09 (-0.24 to 0.07)) and BMI (-0.13 (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000-2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration.

Genetic engineering of microalgae for enhanced lipid production.

Microalgae have the potential to become microbial cell factories for lipid production. Their ability to convert sunlight and CO2 into valuable lipid compounds has attracted interest from cosmetic, biofuel, food and feed industries. In order to make microalgae-derived products cost-effective and commercially competitive, enhanced growth rates and lipid productivities are needed, which require optimization of cultivation systems and strain improvement. Advances in genetic tool development and omics technologies have increased our understanding of lipid metabolism, which has opened up possibilities for targeted metabolic engineering. In this review we provide a comprehensive overview on the developments made to genetically engineer microalgal strains over the last 30 years. We focus on the strategies that lead to an increased lipid content and altered fatty acid profile. These include the genetic engineering of the fatty acid synthesis pathway, Kennedy pathway, polyunsaturated fatty acid and triacylglycerol metabolisms and fatty acid catabolism. Moreover, genetic engineering of specific transcription factors, NADPH generation and central carbon metabolism, which lead to increase of lipid accumulation are also reviewed.

A Single Dose of Marine Chlorella vulgaris Increases Plasma Concentrations of Lutein, ß-Carotene and Zeaxanthin in Healthy Male Volunteers.

The beneficial health effects of Chlorella vulgaris have been associated with the presence of several nutrients and antioxidants, including carotenoids. However, the in vivo bioavailability of Chlorella is still poorly evaluated. In this work, a human intervention study was conducted in 11 healthy men to evaluate the bioavailability of carotenoids within 3 days after the intake of a single dose (6 g) of dried marine Chlorella vulgaris containing lutein (7.08 mg), ß-carotene (1.88 mg) and zeaxanthin (1.47 mg). Subjects were instructed to follow a low carotenoid diet during the experimental phase, starting 1 week earlier. On the day of the experiment, dried microalgae formulated in vegetarian hard capsules were ingested, and blood samples were collected up to 72 h for the analysis of plasma carotenoids concentration by high-performance liquid chromatography with diode-array detection. For all carotenoids, the estimated AUC and Cmax values were significantly different from zero (p < 0.05), indicating that a single dose of marine Chlorella vulgaris increased plasma concentrations of lutein (Cmin-corrected AUC = 1002 µg·h/L, Cmax = 20.4 µg/L), ß-carotene (AUC = 1302 µg·h/L, Cmax = 34.9 µg/L) and zeaxanthin (AUC = 122.2 µg·h/L, Cmax = 3.4 µg/L). The bioavailability of other compounds, namely, polyunsaturated fatty acids and trace elements, was also assessed post-prandial for the first time, showing that linoleic acid, docosahexaenoic acid and iodine were absorbed after microalgae intake. These findings support the use of Chlorella vulgaris as a source of carotenoids, PUFA and essential trace elements with associated health benefits.

Perinatal and Early-Life Nutrition, Epigenetics, and Allergy.

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.

Relationships between inflammatory markers and suicide risk status in major depression.

Pro-inflammatory status has been implicated in depression and suicidal behaviors. Polyunsaturated fatty acids (PUFAs) and cytokines, two types of inflammatory biomarkers, have been associated with suicide, independent of depression severity. How these biomarkers relate to each other is less clear. We measured plasma phospholipid levels of arachidonic acid (AA%), docosahexaenoic acid (DHA%), and eicosapentaenoic acid (EPA%) as a percentage of total phospholipids, as well as serum interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), in 80 patients with major depressive disorder (MDD) and 24 healthy controls (HC). Individual PUFA and cytokine species were compared using ANOVA across four suicide risk-stratified groups: 1) highest-risk, recent (within 5 years) suicide attempters (n = 20); 2) high-risk, severe current suicidal ideators (having intent or plan) with no recent attempt history (n = 22); 3) low-risk, current non-ideators who were also lifetime non-attempters (n = 38); and 4) HC (n = 24). None of the participants were enrolled following an acute suicide attempt. Of biomarkers studied, only DHA% (p = 0.012) and IL-1ß (p = 0.002) differed between groups. In post-hoc testing, DHA% was lower in attempters than ideators (p = 0.018) or MDD non-ideators (trend level, p = 0.073). IL-1ß was lowest in attempters, differentiating them from ideators (p = 0.009) and HC (p = 0.004). Recent suicide attempt, one of the most powerful predictors of suicide risk, was also most closely tied to inflammatory indices in this study. Low DHA% as an indicator of suicide risk is consistent with previous reports; however, lower IL-1ß was unexpected and may relate to acuity/chronicity of inflammation. There is a need for prospective studies of immune status with respect to suicidal behaviors.

Hepatic endoplasmic reticulum calcium fluxes: effect of free fatty acids and KATP channel involvement.

As a common sequel to obesity, plasma and intracellular free fatty acid (FFA) concentrations are elevated and, as a consequence, manifold disturbances in metabolism may ensue. Biochemical processes in the cytosol and organelles, such as mitochondria and endoplasmic reticulum (ER), can be disturbed. In the ER, the maintenance of a high calcium gradient is indispensable for viability. In sarcoplasmic reticulum, selective FFA can induce ER stress by disrupting luminal calcium homeostasis; however, there are limited studies in hepatic microsomes. Our studies found that FFA has a noxious effect on rat hepatic microsomal calcium flux, and the extent of which depended on the number of double bonds and charge. Furthermore, insofar as the FFA had no effect on microsomal calcium efflux, their inhibitory action primarily involves calcium influx. Finally, other cationic channels have been found in hepatic ER, and evidence is presented of their interaction with the Ca2+ ATPase pump.