Polyunsaturated Fatty Acid Metabolism Research Articles

Primary saturation of α, β-unsaturated carbonyl containing fatty acids does not abolish electrophilicity

Metabolism of polyunsaturated fatty acids results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, α,β-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETE) and mono-saturated metabolites of 15-oxoETE and docosahexaenoic acid-derived 17-oxodocosahexaenoinc acid (17-oxoDHA) in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase 1 (PTGR1), known only for its reduction of the α,β-unsaturated double bond, was not responsible for the saturation of oxo-fatty acids at alternative double bonds. Surprisingly, knockdown of PTGR1 expression by shRNA confirmed its participation in the formation of 15-oxoETE and 17-oxoDHA mono-saturated metabolites. Furthermore, overexpression of PTGR1 in A549 cells increased the rate and total amount of oxo-fatty acid saturation. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties.

Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits.

O-147 Differential seminal metabolomic signature is related to sperm quality

Abstract Study question What is the entire metabolomic profile of human semen and does the metabolic composition differ between men with good-quality and low-quality semen? Summary answer Human semen contains ∼700 different metabolites, and the metabolomic signature differs between normozoospermic men and men with altered seminal parameters. What is known already Semen contains a wide diversity of metabolites as has been identified in single and targeted metabolite studies. The full composition of metabolites in human semen, however, is not known. The knowledge of the complete metabolic signature in semen and whether there are differences between metabolic composition and seminal quality could enhance our knowledge of possible factors involved in reduced sperm quality and male infertility. Study design, size, duration Case-control study, where a total of 100 men (age= 29.73±8.9 years) from March 2019 to March 2020 participated. The study was approved by the Ethics Committee of Investigación Biomédica de Andalucia. Participants/materials, setting, methods Semen samples from 69 normozoospermic and 31 oligozoospermic men were collected at the University Hospital and sperm biobank (Ceifer Biobank - NextClinics). The complete metabolome from unprocessed seminal samples was analysed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Raw data were extracted, peak-identified and quality control processed using Metabolon’s hardware and software (metabolon.com). Multiple regression models controlling for age and sample collection centres were applied using R software. Main results and the role of chance In total, 695 different metabolites were detected in the seminal samples, where docosahexaenoate (DHA; 22:6n3, PubChem ID 445580), choline phosphate (1014), dihomo-linolenate (20:3n3 or n6, 5280581), docosapentaenoate (n6 DPA; 22:5n6, 6441454), adenosine 3’,5’-cyclic monophosphate (cAMP, 6076) and N-acetylalliin (122164824) metabolites were the most prevalent. The seminal metabolomic profiles differed significantly between men with normal and low sperm parameters. The most abundant metabolites in normozoospermic men belonged to Lipid Super-Pathway, while Nucleotide Super-Pathway was predominant in semen samples with low quality (p < 0.05). More specifically, the leading Sub-Pathway in normozoospermic men was Long Chain Polyunsaturated Fatty Acid (n3 and n6), whereas Purine and Pyrimidine Metabolism Sub-Pathway prevailed in low-quality semen samples, where DHA and cAMP dominated in men with normal and low seminal quality parameters, respectively (p < 0.05 in all comparisons). Limitations, reasons for caution This is the first study presenting the entire metabolome signature of unprocessed human semen, and these preliminary results need to be confirmed in a bigger sample size. Wider implications of the findings Semen analyses applied in clinics do not evaluate the functional status of sperm, leaving the infertility causes due to male factor frequently unknown. Our study results could help to understand the molecular background of reduced seminal quality and male infertility and lead to identification of molecular biomarkers of functional sperm. Trial registration number not applicable

Freshwater, Landlocked Grand Lake Strain of Atlantic Salmon (Salmo salar L.) as a Potential Genetic Source of Long Chain Polyunsaturated Fatty Acids Synthesis

Selection efforts focused on adaptation to plant-based diets, particularly the ability to synthesize polyunsaturated fatty acids (PUFA), are now emerging in aquaculture. Landlocked salmon (Grand Lake population; GL) may differ from the commercial Saint John River (SJR) strain in terms of PUFA metabolism. The objective of this study was to determine if GL salmon can contribute toward broodstock selection for enhanced PUFA synthesis. Two diets containing either fish oil (FO) or plant-based oil (FO-free) were fed to the SJR and GL strains (∼58 g/fish) for 16 weeks. Growth, liver, and muscle fatty acid (FA) content, and transcript expression of lipid metabolism and inflammation-related genes were evaluated. GL salmon fed the FO diet showed reduced growth compared to SJR salmon (fed either diet); however, GL salmon fed the FO-free diet, growth was not significantly different compared to any group. In liver, SJR salmon fed the FO-free diet had higher levels of n-6 PUFAs (21.9%) compared to GL fed the same diet (15.9%); while GL salmon fed the FO-free diet had higher levels of monounsaturated FAs (48.9%) compared with SJR salmon fed the same diet (35.7%). 20:5n-3 and 22:6n-3 were the same in GL and SJR salmon liver and muscle, respectively, fed the FO-free diet. In liver, GL salmon fed the FO-free diet had higher acac and acly compared to all treatments and had higher fasb compared to both strains fed the FO-diet. GL salmon fed the FO-free diet had higher cd36c and fabp3b in liver compared to GL salmon fed the FO diet and SJR salmon fed either diet. GL salmon fed the FO-free diet had higher lect2a and pgds in liver compared to SJR salmon fed the FO-free diet. In muscle, GL salmon fed the FO-free diet had higher fadsd5 and fadsd6b compared with both strains fed the FO diet. These results suggest there is a genetic basis behind the potential for GL salmon to utilize FO-free diets more efficiently than SJR salmon, with regards to FA metabolism.

Effective Aspirin Treatment of Women at Risk for Preeclampsia Delays the Metabolic Clock of Gestation.

[Figure: see text].

Integrated genomic-metabolic classification of acute myeloid leukemia defines a subgroup with NPM1 and cohesin/DNA damage mutations

Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. Combined serum and urine metabolomics improved AML characterization compared with individual biofluid analysis. At intracellular level, AML displayed dysregulated amino acid, nucleotide, lipid, and bioenergetic metabolism. The integration of intracellular and biofluid metabolomics provided a map of alterations in the metabolism of polyamine, purine, keton bodies and polyunsaturated fatty acids and tricarboxylic acid cycle. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis. Interestingly, integrated genomic-metabolic profiles defined two subgroups of NPM1-mut AML. One was enriched for mutations in cohesin/DNA damage-related genes (NPM1/cohesin-mut AML) and showed increased serum choline + trimethylamine-N-oxide and leucine, higher mutation load, transcriptomic signatures of reduced inflammatory status and better ex-vivo response to EGFR and MET inhibition. The transcriptional differences of enzyme-encoding genes between NPM1/cohesin-mut and NPM1-mut allowed in silico modeling of intracellular metabolic perturbations. This approach predicted alterations in NAD and purine metabolism in NPM1/cohesin-mut AML that suggest potential vulnerabilities, worthy of being therapeutically explored.

Genomic organization and expression pattern of cytochrome P450 genes in the wolf spider Pardosa pseudoannulata

As one of the dominant natural enemies for insect pests, the pond wolf spider, Pardosa pseudoannulata, plays important roles in pest control. Insecticide applications threaten P. pseudoannulata and consequently weaken its control effects. The roles of P450 monooxygenases in insecticide detoxifications have been richly reported in insects, but there are few reported in spiders. In this study, 120 transcripts encoding P. pseudoannulata P450s were identified based on whole genome sequencing. Compared to P450s of Aedes aegypti and Nilaparvata lugens, several novel P450 families were found, such as CYP3310. KEGG analysis of the CYP3310 family indicated that the family might be involved in the synthesis and metabolism of polyunsaturated fatty acids and hydrocarbons. The potential P450s involved in insecticide metabolism were obtained according to the high FPKM values in fat bodies based on transcriptome sequencing. However, none of the selected P450 genes was significantly upregulated by the treatments of deltamethrin or imidacloprid. The present study provides genomic and transcriptomic information of spider P450s, especially for their roles in the synthesis and metabolism of endogenous and exogenous compounds, such as polyunsaturated fatty acids, hydrocarbons and insecticides.

Serum levels of n-3 and n-6 polyunsaturated fatty acids in patients with systemic lupus erythematosus and their association with disease activity: a pilot study

Objective Polyunsaturated fatty acids (PUFAs) may modulate the inflammatory process in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). The aim of this study was to assess the serum concentrations of essential 18-carbon PUFAs and their long-chain derivatives in patients with SLE and healthy controls, and to analyse their associations with laboratory and clinical features of the disease. Method n-6 and n-3 PUFA composition was assessed in the sera of 30 SLE patients and 20 healthy controls using gas chromatography–mass spectrometry. We investigated the associations between PUFAs and disease activity measured with Systemic Lupus Erythematosus Activity Index (SLEDAI) scores, erythrocyte sedimentation rate, C-reactive protein, complement C3 and C4 concentrations, anti-nuclear antibody (ANA) titre, anti-double-stranded DNA (anti-dsDNA) antibody concentration, and medications. Results Serum linoleic acid (LA) and α-linolenic acid concentrations were significantly higher in SLE patients compared with healthy controls. LA concentration correlated positively with the ANA titre and corticosteroid doses; eicosapentaenoic acid (EPA) and docosahexaenoic acid correlated inversely with anti-dsDNA antibody concentration. Patients treated with immunosuppressants had significantly lower concentrations of LA, arachidonic acid, and EPA. Conclusion Both n-6 and n-3 PUFA precursors can participate in the inflammatory process in SLE patients. The mechanism of the PUFA metabolism disturbance needs further exploration.

Non-enzymatic lipid peroxidation initiated by photodynamic therapy drives a distinct ferroptosis-like cell death pathway

Ferroptosis is primarily triggered by a failure of the glutathione (GSH)-glutathione peroxidase 4 (GPX4) reductive system and associated overwhelming lipid peroxidation, in which enzymes regulating polyunsaturated fatty acid (PUFA) metabolism, and in particular acyl-CoA synthetase long chain family member 4 (ACSL4), are central. Here, we found that exogenous oxygen radicals generated by photodynamic therapy (PDT) can directly peroxidize PUFAs and initiate lipid autoxidation, coinciding with cellular GSH depletion. Different from canonical ferroptosis induced by RSL3 or erastin, PDT-initiated lipid peroxidation and ferroptotis-like cell death is independent of lipoxygenase (ALOXs) and ACSL4. Especially, this form of cell death modality can be triggered in malignant cells insensitive to or acquired resistance to canonical ferroptosis inducers. We also observed a distinct iron metabolism pathway in this PDT-triggered cell death modality, in which cytosolic labile iron is decreased probably due to its relocation to mitochondria. Inhibition of the mitochondrial Ca2+ and Fe2+ uniporter (MCU) effectively prevented PDT-triggered lipid peroxidation and subsequent cell death. Therefore, we tentatively term this distinct ferroptosis-like cell death as liperoptosis. Moreover, using the clinically approved photosensitizer Verteporfin, PDT inhibited tumor growth through inducing prevailing ferroptosis-like cell death in a mouse xenograft model. With its site-specific advantages, these findings highlight the value of using PDT to trigger lipid peroxidation and ferroptosis-like cell death in vivo, and will benefit exploring the exact molecular mechanism of immunological effects of PDT in cancer treatment.

MicroRNA-mRNA Regulatory Networking Fine-Tunes Polyunsaturated Fatty Acid Synthesis and Metabolism in the Inner Mongolia Cashmere Goat.

Fatty acid composition is an important aspect of meat quality in ruminants. Improving the beneficial fatty acid level in cashmere goat meat is important to its economic value. To investigate microRNAs (miRNAs) and mRNAs that regulate or coregulate polyunsaturated fatty acid (PUFA) synthesis and metabolism in the Inner Mongolia cashmere goat, we used longissimus dorsi muscle (WLM) and biceps femoris muscle (WBM) for transcript-level sequencing. RT-qPCR was used to evaluate the expression of mRNAs and miRNAs associated with PUFA synthesis and metabolism. The total PUFA content in the WBM was significantly higher than that in the WLM (P < 0.05). Our study is the first to systematically report miRNAs in cashmere goat meat. At the mRNA level, 20,375 genes were identified. ACSL1, CD36 and TECRL were at the center of a gene regulatory network and contributed significantly to the accumulation and metabolic regulation of fatty acids. At the miRNA level, 426 known miRNAs and 30 novel miRNAs were identified. KEGG analysis revealed that the miRNA target genes were involved mainly in the PPAR signaling pathway. The mRNA-miRNA coregulation analysis showed that ACSL1 was negatively targeted by nine miRNAs: chi-miR-10a-5p, chi-miR-10b-5p, chi-miR-130b-5p, chi-miR-15a-5p_R-1, chi-miR-15b-5p, chi-miR-16a-5p, chi-miR-16b-5p, chi-miR-181c-5p_R+1, and chi-miR-26b-5p. Finally, we speculated that the simultaneous silencing of ACSL1 by one or more of these nine miRNAs through PPAR signaling led to low ACSL1 expression in the WLM and, ultimately to high PUFA content in the WBM. Our study helps elucidate the metabolic regulation of fatty acids in Inner Mongolia cashmere goats.

Associations Between Vitamin B6 Status and Plasma Polyunsaturated Fatty Acids Among US Older Adults: NHANES 2003–2004

ObjectivesPrevious evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP < 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. MethodsA cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. ResultsPlasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8–2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0–4.33, P = 0.049, respectively]. ConclusionsIn US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding SourcesNo funding sources.

Differential modulation of polyunsaturated fatty acids in patients with myocardial infarction treated with ticagrelor or clopidogrel

SummaryUntargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P2Y12 inhibitors. We identified a signature that discriminates patients, which involves polyunsaturated fatty acids (PUFAs) and particularly the omega-3 fatty acids docosahexaenoate and eicosapentaenoate. The known cardiovascular benefits of PUFAs could contribute to the efficacy of ticagrelor. Our work, beyond pointing out the high relevance of untargeted metabolomics in evaluating response to treatment, establishes PUFA metabolism as a pathway of clinical interest in the recovery path from MI.

Targeted Metabolic Profiling and PRM Analysis of Proteins Revealed Impaired Polyunsaturated Fatty Acid Metabolism and GTP Metabolism in the Brainstem of Spontaneously Hypertensive Rats.

An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs (n = 8, 11 weeks old) and normotensive Wistar rats (n = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis-11,14-eicosadienoic acid, cis-13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase (p < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP (p < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs (p < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.

High Glucose Shifts the Oxylipin Profiles in the Astrocytes towards Pro-Inflammatory States.

Hyperglycemia is associated with several complications in the brain, which are also characterized by inflammatory conditions. Astrocytes are responsible for glucose metabolism in the brain and are also important participants of inflammatory responses. Oxylipins are lipid mediators, derived from the metabolism of polyunsaturated fatty acids (PUFAs) and are generally considered to be a link between metabolic and inflammatory processes. High glucose exposure causes astrocyte dysregulation, but its effects on the metabolism of oxylipins are relatively unknown and therefore, constituted the focus of our work. We used normal glucose (NG, 5.5 mM) vs. high glucose (HG, 25 mM) feeding media in primary rat astrocytes-enriched cultures and measured the extracellular release of oxylipins (UPLC-MS/MS) in response to lipopolysaccharide (LPS). The sensitivity of HG and NG growing astrocytes in oxylipin synthesis for various serum concentrations was also tested. Our data reveal shifts towards pro-inflammatory states in HG non-stimulated cells: an increase in the amounts of free PUFAs, including arachidonic (AA), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, and cyclooxygenase (COX) mediated metabolites. Astrocytes cultivated in HG showed a tolerance to the LPS, and an imbalance between inflammatory cytokine (IL-6) and oxylipins release. These results suggest a regulation of COX-mediated oxylipin synthesis in astrocytes as a potential new target in treating brain impairment associated with hyperglycemia.

Metabolism of Dietary Polyunsaturated Fatty Acids Modulates Healthspan of C. elegans

Dietary omega-3 and omega-6 unsaturated fatty acids (UFAs) are essential for normal man physiological processes in multiple organisms. However, their mechanism(s) that drive these processes remain largely unknown. Recent studies showed that downstream metabolites of UFAs play a critical role in inflammation, blood pressure regulation, pain perception, carcinogenesis, wound healing, and tissue and neural repair. Here, we hypothesize that the metabolites of dietary UFAs affect both development and aging. To study the role and underlying mechanism of the effect of UFA metabolites on the healthspan of organisms, we used C. elegans as a model organism because 1) C. elegans has been wildly used for aging study; 2) The C. elegans genome is highly conserved; 3) genetic modifications are relatively easy; 4) vast community resources are available for minimum cost or free and 5) genetic tools are largely available. As a result, this model organism greatly facilitates the mechanistic investigation of the effects of UFA metabolites. In this specific presentation, we will present metabolomic data obtained from the state-of-the-art ultra-performance liquid chromatography coupled with tandem mass spectrometry to demonstrate that C. elegans produces similar classes of UFA metabolites comparable to humans and mammals, and the endogenous levels of cytochrome P450 (CYP) metabolites of UFA change with the age of C. elegans. We will also present the effect of treatment with CYP UFA metabolites or modulation of UFA CYP metabolism on aging (lifespan and thrashing assay), reproduction (egg laying and egg viability assay) and neurodevelopment (fluorescent imaging). In conclusion, our results indicate that UFA metabolites play important physiological roles in C. elegans, and future mechanistic studies will also be discussed.

Effect of fat diet on essential fatty acid metabolism of neutral lipids in rat blood serum

Aim. To determine the effect of dietary fats on the content and metabolism of polyunsaturated fatty acids (PUFA) in the fraction of neutral lipids blood serum.Methods. The effect of sunflower, high oleic sunflower (HOSO) and palm oils was studied when feeding rats with diets with 5 % fat for 30 days. Rats fed a fat-free diet (FFD) served as a control. The fatty acid composition of neutral blood serum lipids was determined by gas chromatography. The “activity” of fatty acid biosynthesis enzymes: elongase and desaturases was calculated from the ratio of the content of fatty acids.Results. A high content of PUFA was found in rats treated with FFD. Feeding rats with a diet with 5 % sunflower oil increased the total content of PUFAs with a slight decrease in the level of ω-3 PUFAs. Feeding rats with diets containing 5 % palm oil or HOSO did not affect the total content of PUFA, but increased the content of ω-3 PUFA. A very high "activity" of stearyl-CoA desaturase was found in rats fed FFD and fat diets. The consumption of HOSO inhibits the formation of arachidonic acid, while the consumption of palm oil enhances it.Conclusions. A high level of PUFA in neutral lipids in the blood serum of rats may indicate the presence of endogenous sources of PUFA. The optimal (for rats) consumption of dietary fats has a small effect on the content and metabolism of PUFA, with the exception of sunflower oil, the consumption of which significantly increases the ω-6/ω-3 PUFA ratio.

Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineated in the different organs. The liver showed an oxidant/antioxidant profile and lipid pathways widely modulated by PUFA and vitamin E administration; on the other hand, the testis’ oxidative profile rather than its lipid profile seemed to be particularly affected, an outcome opposite to that of the brain (modulation operated by dietary PUFA).

Serum Soluble Epoxide Hydrolase Related Oxylipins and Depression in Patients With Type 2 Diabetes: An Exploratory Lipidomic Study

Type 2 diabetes mellitus (T2DM) carries an increased risk for depression. Perturbations in polyunsaturated fatty acid (PUFA) metabolism have been observed in depression and T2DM. PUFAs can be converted by cytochrome P450 epoxygenases (CYP450s) into epoxides, which resolve inflammation, and epoxides are metabolized by soluble epoxide hydrolase (sEH) into inactive or cytotoxic diols. Here, we survey these epoxide and diol “oxylipins” in T2DM patients with and without depression.

Targeting a Braf/Mapk pathway rescues podocyte lipid peroxidation in CoQ-deficiency kidney disease.

Mutations affecting mitochondrial coenzyme Q (CoQ) biosynthesis lead to kidney failure due to selective loss of podocytes, essential cells of the kidney filter. Curiously, neighboring tubular epithelial cells are spared early in disease despite higher mitochondrial content. We sought to illuminate noncanonical, cell-specific roles for CoQ, independently of the electron transport chain (ETC). Here, we demonstrate that CoQ depletion caused by Pdss2 enzyme deficiency in podocytes results in perturbations in polyunsaturated fatty acid (PUFA) metabolism and the Braf/Mapk pathway rather than ETC dysfunction. Single-nucleus RNA-Seq from kidneys of Pdss2kd/kd mice with nephrotic syndrome and global CoQ deficiency identified a podocyte-specific perturbation of the Braf/Mapk pathway. Treatment with GDC-0879, a Braf/Mapk-targeting compound, ameliorated kidney disease in Pdss2kd/kd mice. Mechanistic studies in Pdss2-depleted podocytes revealed a previously unknown perturbation in PUFA metabolism that was confirmed in vivo. Gpx4, an enzyme that protects against PUFA-mediated lipid peroxidation, was elevated in disease and restored after GDC-0879 treatment. We demonstrate broader human disease relevance by uncovering patterns of GPX4 and Braf/Mapk pathway gene expression in tissue from patients with kidney diseases. Our studies reveal ETC-independent roles for CoQ in podocytes and point to Braf/Mapk as a candidate pathway for the treatment of kidney diseases.

Incorporation of Dietary Arachidonic and Docosatetraenoic Acid into Mouse Brain.

It is essential to analyze the metabolism of dietary polyunsaturated fatty acids in the brain for the research and development of functional foods. In this study, a single dose of 2,2-dideuterium-labeled docosatetraenoic acid ((+2)DTA) or 2,2-dideuterium-labeled arachidonic acid ((+2)AA) was orally administered to Institute of Cancer Research (ICR) mice and its metabolism in the brain was investigated. In the (+2)DTA group, the (+2)DTA content in the brain was significantly increased at 4, 8, 24, and 96 h compared to 0 h after administration, while in the (+2)AA group, the (+2)AA content was significantly increased at 4, 8, 24, and 96 h compared to 0 h. However, there was no significant difference in the content of (+2)DTA, a metabolite of (+2)AA, among all the groups. These results suggest that dietary (+2)DTA and (+2)AA pass through the blood-brain barrier and dietary (+2)AA is rather stored in the brain than converted to (+2)DTA.