Stereoselective Syntheses of Polyunsaturated Fatty Acids, 13-(S)-HODE and 15-(S)-HETE.

Polyunsaturated fatty acids and their metabolites have been reported in which their pathway has potential for the modulation of cancer cell growth. 13-(S)-HODE and 15-(S)-HETE, both of which are main metabolites of 15-LOXs, play an important role as endogenous ligands in biological systems. However, the modification of 13-(S)-HODE and 15-(S)-HETE in pharmaceutical applications has not been explored widely. Herein, we report the stereoselective syntheses of 13-(S)-HODE, 15-(S)-HETE, and its derivatives to enable the synthesis of bioactive fatty acid analogues.

Dietary n-3 alpha-linolenic and n-6 linoleic acids modestly lower serum lipoprotein(a) concentration but differentially influence other atherogenic lipoprotein traits: A randomized trial.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal, genetically determined cardiovascular risk factor. Limited evidence suggests that dietary unsaturated fat may increase serum Lp(a) concentration by 10-15 %. Linoleic acid may increase Lp(a) concentration through its endogenous conversion to arachidonic acid, a process regulated by the fatty acid desaturase (FADS) gene cluster. We aimed to compare the Lp(a) and other lipoprotein trait-modulating effects of dietary alpha-linolenic (ALA) and linoleic acids (LA). Additionally, we examined whether FADS1 rs174550 genotype modifies Lp(a) responses. METHODS: A genotype-based randomized trial was performed in 118 men homozygous for FADS1 rs174550 SNP (TT or CC). After a 4-week run-in period, the participants were randomized to 8-week intervention diets enriched with either Camelina sativa oil (ALA diet) or sunflower oil (LA diet) 30-50 mL/day based on their BMI. Serum lipid profile was measured at baseline and at the end of the intervention. RESULTS: ALA diet lowered serum Lp(a) concentration by 7.3 % (p = 0.003) and LA diet by 9.5 % (p < 0.001) (p = 0.089 for between-diet difference). Both diets led to greater absolute decreases in individuals with higher baseline Lp(a) concentration (p < 0.001). Concentrations of LDL cholesterol (LDL-C), non-HDL-C, remnant-C, and apolipoprotein B were lowered more by the ALA diet (p < 0.01). Lipid or lipoprotein responses were not modified by the FADS1 rs174550 genotype. CONCLUSIONS: A considerable increase in either dietary ALA or LA from vegetable oils has a similar Lp(a)-lowering effect, whereas ALA may lower other major atherogenic lipids and lipoproteins to a greater extent than LA. Genetic differences in endogenous PUFA conversion may not influence serum Lp(a) concentration.

The versatile CYP74 clan enzyme CYP440A19 from the European lancelet Branchiostoma lanceolatum biosynthesizes novel macrolactone, epoxydiene, and related oxylipins.

The present work reports the detection and cloning of a new CYP74 clan gene of the European lancelet (Branchiostoma lanceolatum) and the biochemical characterization of the recombinant protein CYP440A19. CYP440A19 possessed epoxyalcohol synthase (EAS) activity towards the 13-hydroperoxides of linoleic and α-linolenic acids, which were converted into oxiranylcarbinols, i.e., (11S,12R,13S)-11-hydroxy-12,13-epoxy derivatives. The conversion of 9-hydroperoxides produced distinct products. Linoleic acid 9(S)-hydroperoxide (9-HPOD) was mainly converted into 9,14-diol (10E,12E)-9,14-dihydroxy-10,12-octadecadienoic acid and macrolactone 9(S),10(R)-epoxy-11(E)-octadecen-13(S)-olide. In addition, (8Z)-colneleic acid was formed. Brief incubations of the enzyme with 9-HPOD in a biphasic system of hexane-water enabled the isolation of the short-lived 9,10-epoxydiene (9S,10R,11E,13E)-9,10-epoxy-11,13-octadecadienoic acid. The structure and stereochemistry of the epoxyalcohols, macrolactone, (8Z)-colneleic acid (Me), and 9,10-epoxydiene (Me) were confirmed by 1H-NMR, 1H-1H-COSY, 1H-13C-HSQC, and 1H-13C-HMBC spectroscopy. Macrolactone and cis-9,10-epoxydiene are novel products. The 9-hydroperoxide of α-linolenic acid was mainly converted into macrolactone 9(S),10(R)-epoxy-11(E),15(Z)-octadecadiene-13(S)-olide and a minority of divinyl ethers, particularly (8Z)-colnelenic acid. The versatility of enzyme catalysis, as well as the diversity of CYP74s and other enzymes involved in oxylipin biosynthesis, demonstrates the complexity of the lipoxygenase pathway in lancelets.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. MATERIALS AND METHODS: Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. RESULTS: Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. CONCLUSION: Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption.

INTRODUCTION: Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients. METHODS: An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients. RESULTS: Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal. DISCUSSION: The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.

The Use of Evening Primrose Oil for Cervical Ripening in Low-Risk Women with Term Pregnancy: A Randomized Double-Blinded Controlled Trial.

BACKGROUND: Several methods have been developed for cervical ripening. The data regarding the efficiency of evening primrose oil (EPO) are inconsistent. The purpose of this study was to investigate the outcomes of EPO use on cervical ripening in low-risk women with term pregnancy. PATIENTS AND METHODS: Low-risk term pregnant women referred to the obstetrics clinic of Imam Hossein Hospital in Tehran who were eligible according to the inclusion were randomized either to the case or control group. The case group received 1,000 mg vaginal EPO capsule, and the other group received a vaginal placebo capsule daily, similar to the original drug. The primary outcome was Bishop score, while the duration of labor phases and the inducing procedures were the secondary outcomes. RESULTS: Forty-eight participants were randomized to each group and were considered for data analysis. Although Bishop score was not statistically different before the intervention, it was significantly higher in case group compared to the placebo group after the intervention (EPO = 5.83 ± 1.68, placebo = 5.19 ± 1.52, p value = 0.002). Four participants in the case group and two in the control group underwent cesarean section (p value = 0.677). The need for labor induction was significantly higher in the placebo group than EPO group (oxytocin injection: 10.4% vs. 31.3%, p value = 0.012, amniotomy: 75% vs. 41.7, p value = 0.001). CONCLUSION: The vaginal use of EPO could be considered as a safe and efficient approach for cervical ripening in low-risk term pregnant women.Es wurden verschiedene Methoden zur Zervixreifung entwickelt. Die Daten zur Wirksamkeit von Nachtkerzenöl (evening primrose oil, EPO) sind uneinheitlich. Mit dieser Studie sollen die Ergebnisse der Anwendung von EPO zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft untersucht werden.Schwangere Frauen mit niedrigem Risiko und termingerechter Schwangerschaft, die in die Geburtsklinik des Imam-Hossein-Krankenhauses in Teheran eingewiesen wurden und gemäss den Einschlusskriterien für die Teilnahme infrage kamen, wurden randomisiert der Fall- oder der Kontrollgruppe zugewiesen. Die Fallgruppe erhielt 1.000 mg EPO als Vaginalkapseln, während die andere Gruppe täglich eine vaginale Placebokapsel erhielt, die dem Originalpräparat ähnelte. Primäres Zielkriterium war der Bishop-Score und sekundäre Zielkriterien waren die Dauer der Wehenphasen sowie die Verfahren zur Geburtseinleitung.Jeder Gruppe wurden randomisiert 48 Teilnehmerinnen zugewiesen und bei der Datenanalyse berücksichtigt. Während vor der Intervention kein statistisch signifikanter Unterschied im Bishop-Score bestand, fiel dieser nach der Intervention in der Fallgruppe signifikant höher aus als in der Placebogruppe (EPO = 5,83 ± 1,68, Placebo = 5,19 ± 1,52, p-Wert = 0,002). Bei vier Teilnehmerinnen in der Fallgruppe und zwei in der Kontrollgruppe wurde ein Kaiserschnitt durchgeführt (p-Wert = 0,677). Die Notwendigkeit einer Weheneinleitung war in der Placebogruppe signifikant höher als in der EPO-Gruppe (Oxytocin-Injektion: 10,4% vs. 31,3%, p-Wert = 0,012, Amniotomie: 75% vs. 41,7%, p-Wert = 0,001).Die vaginale Anwendung von EPO kann als sicherer und wirksamer Ansatz zur Zervixreifung bei Frauen mit niedrigem Risiko und termingerechter Schwangerschaft angesehen werden.

The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials.

BACKGROUND: Evening primrose oil (EPO), extracted from the seeds of Oenothera biennis, has gained attention for its therapeutic effects in various inflammatory conditions. METHOD: We performed a systematic search in multiple databases and defined the inclusion criteria based on the following PICOs: P: Patients with a form of inflammatory condition, I: EPO, C: Placebo or other therapeutic interventions, O: changes in inflammatory markers or patients' symptoms; S: randomized controlled trials. The quality of the RCTs was evaluated using Cochrane's RoB tool. RESULTS: Several conditions were investigated in the literature. In rheumatoid arthritis, mixed results were observed, with some studies reporting significant improvements in symptoms while others found no significant impact. EPO showed some results in diabetes mellitus, atopic eczema, menopausal hot flashes, and mastalgia. However, it did not demonstrate effectiveness in chronic hand dermatitis, tardive dyskinesia, psoriatic arthritis, cystic fibrosis, hepatitis B, premenstrual syndrome, contact lens-associated dry eyes, acne vulgaris, breast cyst, pre-eclampsia, psoriasis, or primary Sjogren's syndrome. Some results were reported from multiple sclerosis after EPO consumption. Studies in healthy volunteers indicated no significant effect of EPO on epidermal atrophy, nevertheless, positive effects on the skin regarding hydration and barrier function were achieved. CONCLUSION: Some evidence regarding the potential benefits of EPO in inflammatory disorders were reported however caution is due to the limitations of the current survey. Overall, contemporary literature is highly heterogeneous and fails to provide strong recommendations regarding the efficacy of EPO on inflammatory disorders. Further high-quality studies are necessitated to draw more definite conclusions and establish O. biennis oil effectiveness as an assuring treatment option in alleviating inflammatory conditions.

Biochar and conservation tillage affect the agronomic performance and fatty acid composition of Nigella sativa L. under both irrigated and dryland conditions.

Soils in arid and semi-arid regions like Iran have suffered greatly from low organic matter content and low water availability. Traditional tillage and the overuse of chemical fertilizers are accelerating the problems in the region. So, sensible and sustainable strategies such as conservation tillage and natural organic inputs are becoming increasingly important to enhance organic matter and humidity in the soil and grow high-quality crops in agroecosystems. Thus, in 2019 and 2020, a split-split plot arrangement within a randomized complete block design was conducted in Iran to assess the effects of irrigated conditions, tillage systems, and biochar on the aforementioned traits. There were two irrigation conditions (irrigated and dryland) as the main plots, three tillage methods (conventional, minimum, and no-tillage) as sub-plots, and two application rates for biochar (0 and 15 ton ha-1) as sub-sub plots. The findings indicated that biochar application enhanced grain yield across all tillage methods under both irrigation conditions. Biochar with minimum tillage improved oil yield by 23% and 29% compared to those that did not use biochar under the dryland and irrigated conditions, respectively. Moreover, oil yield was higher in 2020 than in 2019 for all tillage systems and biochar rates. The main components of Nigella sativa L. oil belong to linoleic, oleic, and palmitic acids. Minimum tillage with biochar under irrigated conditions in 2020 and no-tillage without biochar under dryland conditions in 2019 had the most (59%) and the least linoleic acid (53%), respectively. Conventional, minimum, and no-tillage with biochar in dryland conditions significantly increased linoleic acid by 2%, 3%, and 5% compared to those without biochar in 2020, respectively. In general, adopting biochar with minimum tillage produced the best outcomes for Nigella sativa L. yield, and grain oil quality under both irrigation conditions. It is recommended that farmers incorporate these practices to produce high-quality Nigella sativa L. in sustainable agricultural systems.

Oleic and linoleic acids promote chondrocyte apoptosis by inhibiting autophagy via downregulation of SIRT1/FOXO1 signaling.

Osteoarthritis (OA) is a complex joint disease that currently has no cure. OA involves metabolic disorders in chondrocytes and an imbalance between autophagy and apoptosis. As a common risk factor for OA, obesity induces changes in the fatty acid composition of synovial fluid, thereby disturbing chondrocyte homeostasis. However, whether unsaturated fatty acids affect the development of OA by regulating chondrocyte autophagy remains unclear. This study aimed to determine the effects of oleic and linoleic acids on chondrocyte autophagy and related mechanisms. Based on the mass spectrometry results, the levels of multiple unsaturated fatty acids, including oleic and linoleic acids, in the synovial fluid of patients with OA and obesity were significantly higher than those in patients with OA only. Moreover, we found that FOXO1 and SIRT1 were downregulated after oleic and linoleic acids treatment of chondrocytes, which inhibited chondrocyte autophagy. Importantly, the upregulation of SIRT1 and FOXO1 expression not only increased the level of autophagy but also improved the expression of chondrocyte extracellular matrix proteins. Furthermore, upregulated SIRT1 and FOXO1 expression alleviated the destruction of the articular cartilage in an OA rat model. Our results suggest that SIRT1/FOXO1 signaling can alleviate oleic acid- and linoleic acid-induced cartilage degradation both in vitro and in vivo and that the SIRT1/FOXO1 pathway may serve as an effective treatment target for inhibiting OA progression.

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1ß, and IL-6 pathway.

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1ß, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1ß, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-ß and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

Can humans smell tastants?

Although studies have shown that olfaction may contribute to the perception of tastant, literature is scarce or circumstantial, especially in humans. This study aims to (i) explore whether humans can perceive solutions of basic prototypical tastants through orthonasal and retronasal olfaction and (ii) to examine what volatile odor compounds (VOCs) underlie this ability. Solutions of 5 basic tastants (sucrose, sodium chloride, citric acid, monosodium glutamate [MSG], quinine) dissolved in water, and 2 fatty acids (oleic and linoleic acid) dissolved in mineral oil were prepared. Triangle discrimination tests were performed (n = 41 in duplicate) to assess whether the tastant solutions can be distinguished from blanks (solvents) through ortho- and retronasal olfaction. Participants were able to distinguish all tastant solutions from blank through orthonasal olfaction. Only sucrose, sodium chloride, oleic acid, and linoleic acid were distinguished from blank by retronasal olfaction. Ethyl dichloroacetate, methylene chloride, and/or acetone were identified in the headspace of sucrose, MSG, and quinine solutions but not in the headspace of water, sodium chloride, and citric acid solutions. Fat oxidation compounds such as alcohols and aldehydes were detected in the headspace of the oleic and linoleic acid solutions but not the mineral oil. We conclude that prototypical tastant solutions can be discriminated from water and fatty acid solutions from mineral oil through orthonasal olfaction. Differences in the volatile headspace composition between blanks and tastant solutions may have facilitated the olfactory discrimination. These findings can have methodological implications for future studies assessing gustatory perception using these prototypical taste compounds.

The inhibitory effects of live and UV-killed Akkermansia muciniphila and its derivatives on cytotoxicity and inflammatory response induced by Clostridioides difficile RT001 in vitro.

Clostridioides difficile infection (CDI) is the leading cause of healthcare-acquired infections worldwide. Probiotics are widely recommended to prevent CDI and its recurrences. Akkermansia muciniphila, as a therapeutic symbiont colonizing the intestinal mucosal layer, is considered to be a promising next-generation probiotic. In this work, we assessed the inhibitory effects of A. muciniphila MucT and its derivatives on cytotoxicity and inflammatory response induced by C. difficile RT001 in Caco-2 cells. The results obtained from SEM revealed that the morphology of UV-killed A. muciniphila remained unchanged after UV inactivation. TEM analysis showed that A. muciniphila-isolated extracellular vesicles (EVs) were spherical and ranged from 50 to 200 nm in size. Toxigenic supernatant (Tox-S) of C. difficile RT001 (500 µg/ml) significantly (P <0.01) reduced the cell viability of Caco-2 cells. Caco-2 cells treated with live (MOI 10), UV-killed (MOI 10), cell-free supernatant (CFS, 106 cfu/ml), and EVs (20 µg/ml) of A. muciniphila exhibited over 90% viability in comparison to untreated control. The neutralized CFS preparation using A. muciniphila and its derivatives could notably reduce the expression level of inflammatory markers. Additionally, A. muciniphila and its derivatives modulated the production of IL-1ß, TNF-α, and IL-10 in Tox-S stimulated Caco-2 cells. We demonstrated that A. muciniphila and its derivatives can modulate changes in the gut barrier-related genes and inflammatory response caused by C. difficile Tox-S in Caco-2 cells.

Impaired Reverse Cholesterol Transport is Associated with Changes in Fatty Acid Profile in Children and Adolescents with Abdominal Obesity.

BACKGROUND: Abdominal obesity is an important cardiovascular disease risk factor. Plasma fatty acids display a complex network of both pro and antiatherogenic effects. High density lipoproteins (HDL) carry out the antiatherogenic pathway called reverse cholesterol transport (RCT), which involves cellular cholesterol efflux (CCE), and lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. OBJECTIVES: Our aim was to characterize RCT and its relation to fatty acids present in plasma in pediatric abdominal obesity. METHODS: Seventeen children and adolescents with abdominal obesity and 17 healthy controls were studied. Anthropometric parameters were registered. Glucose, insulin, lipid levels, CCE employing THP-1 cells, LCAT and CETP activities, plus fatty acids in apo B-depleted plasma were measured. RESULTS: The obese group showed a more atherogenic lipid profile, plus lower CCE (Mean±Standard Deviation) (6 ± 2 vs. 7 ± 2%; P < 0.05) and LCAT activity (11 ± 3 vs. 15 ±5 umol/dL.h; P < 0.05). With respect to fatty acids, the obese group showed higher myristic (1.1 ± 0.3 vs. 0.7 ± 0.3; P < 0.01) and palmitic acids (21.5 ± 2.8 vs. 19.6 ± 1.9; P < 0.05) in addition to lower linoleic acid (26.4 ± 3.3 vs. 29.9 ± 2.6; P < 0.01). Arachidonic acid correlated with CCE (r = 0.37; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05), palmitioleic acid with CCE (r = -0.35; P < 0.05), linoleic acid with CCE (r = 0.37; P < 0.05), lauric acid with LCAT (r = 0.49; P < 0.05), myristic acid with LCAT (r = -0.37; P < 0.05) ecoisatrienoic acid with CCE (r = 0.40; P < 0.05) and lignoseric acid with LCAT (r = -0.5; P < 0.01). CONCLUSIONS: Children and adolescents with abdominal obesity presented impaired RCT, which was associated with modifications in proinflammatory fatty acids, such as palmitoleic and myristic, thus contributing to increased cardiovascular disease risk.

Analysis of changes in volatile compounds and evolution in free fatty acids, free amino acids, nucleotides, and microbial diversity in tilapia (Oreochromis mossambicus) fillets during cold storage.

BACKGROUND: Aquatic products are rich in nutrients and unique in flavor, and are popular among the public. However, aquatic products are extremely susceptible to quality degradation during storage, of which odor deterioration is the most obvious and influential aspect. Odor deterioration in aquatic products is widespread and severely affects overall flavor and quality. In this study, odor deterioration and flavor-related quality degradation of tilapia during cold storage are discussed, focusing on the changes in volatile compounds and the evolution of free fatty acids (FFAs), free amino acids (FAAs), nucleotides, and microbial diversity. RESULTS: A total of 63 volatile compounds were detected by gas chromatography-mass spectrometry, including 11 hydrocarbons, 10 alcohols, 6 aldehydes, 8 ketones, 6 esters, 9 aromatics, 3 phenols, and 10 other compounds. Microbial diversity analysis revealed that Acinetobacter, Psychrobacter, Vagococcus, and Myroides were the main dominant species of tilapia at the end of cold storage and predicted that microorganisms could influence the flavor of tilapia by participating in important metabolic pathways. Meanwhile, the evolution of FFAs, FAAs, and nucleotides also had a significant impact on odor deterioration, as evidenced by the contribution of unsaturated fatty acids (such as oleic acid and linoleic acid), Lys, and off-flavor nucleotides (HxR and Hx) to the undesirable flavor. Oxidation of oleic acid and linoleic acid resulted in changes in aldehydes, with Lys, HxR, and Hx being key flavor precursors and off-flavor contributors. CONCLUSION: This study contributes to a comprehensive overview of odor deterioration and the evolution of flavor-related quality in tilapia during cold storage, providing new insights into the regulation of overall flavor and quality. © 2023 Society of Chemical Industry.

Consuming a Linoleate-Rich Diet Increases Concentrations of Tetralinoleoyl Cardiolipin in Mouse Liver and Alters Hepatic Mitochondrial Respiration.

BACKGROUND: Hepatic mitochondrial dysfunction is a major cause of fat accumulation in the liver. Individuals with fatty liver conditions have hepatic mitochondrial structural abnormalities and a switch in the side chain composition of the mitochondrial phospholipid, cardiolipin, from poly- to monounsaturated fatty acids. Linoleic acid (LA), an essential dietary fatty acid, is required to remodel nascent cardiolipin (CL) to its tetralinoleoyl cardiolipin (L4CL, CL with 4 LA side chains) form, which is integral for mitochondrial membrane structure and function to promote fatty acid oxidation. It is unknown, however, whether increasing LA in the diet can increase hepatic L4CL concentrations and improve mitochondrial respiration in the liver compared with a diet rich in monounsaturated and saturated fatty acids. OBJECTIVES: The main aim of this study was to test the ability of a diet fortified with LA-rich safflower oil (SO), compared with the one fortified with lard (LD), to increase concentrations of L4CL and improve mitochondrial respiration in the livers of mice. METHODS: Twenty-four (9-wk-old) C57 BL/J6 male mice were fed either the SO or LD diets for ∼100 d, whereas food intake and body weight, fasting glucose, and glucose tolerance tests were performed to determine any changes in glycemic control. RESULTS: Livers from mice fed SO diet had higher relative concentrations of hepatic L4CL species compared with LD diet-fed mice (P value = 0.004). Uncoupled mitochondria of mice fed the SO diet, compared with LD diet, had an increased baseline oxygen consumption rate (OCR) and succinate-driven respiration (P values = 0.03 and 0.01). SO diet-fed mice had increased LA content in all phospholipid classes compared with LD-fed mice (P < 0.05). CONCLUSIONS: Our findings reveal that maintaining or increasing hepatic L4CL may result in increased OCR in uncoupled hepatic mitochondria in healthy mice whereas higher oleate content of CL reduced mitochondrial function shown by lower OCR in uncoupled mitochondria.

Mechanisms of the Formation of Nonvolatile and Volatile Oxidation Products from Methyl Linoleic Acid at High Temperatures.

The impact of the oxidation of linoleic acid cannot be overlooked in daily food consumption. This study used gas chromatography-mass spectrometry (GC-MS) to identify both nonvolatile oxidation products and volatile oxidation products of methyl linoleic acid at 180 °C and density function theory to investigate oxidation mechanisms. An analysis of nonvolatile oxidation products revealed the presence of three primary oxidation products. The three primary oxidation products were identified as hydroperoxides, peroxide-linked dimers, and heterocyclic compounds in a ratio of 2.70:1:3.69 (mmol/mmol/mmol). The volatile components of secondary oxidation products were found including aldehydes (40.77%), alkanes (19.89%), alcohols (9.02%), furans (6.11%), epoxides (0.46%), and acids (2.50%). DFT calculation proved that the secondary oxidation products mainly came from peroxides (77%). Finally, we look forward to our research contributing positively to lipid autoxidation and human health.

Elucidation for the pharmacological effects and mechanism of Shen Bai formula in treating myocardial injury based on energy metabolism and serum metabolomic approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated. AIM OF THE STUDY: In present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury. MATERIALS AND METHODS: Through energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism. RESULTS: Results showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J2 (PGJ2), 15-deoxy-Δ-12,14-PGJ2, 15-keto-PGE2, 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism. CONCLUSION: We successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis.

Cholesterol is more readily oxidized than phospholipid linoleates in cell membranes to produce cholesterol hydroperoxides.

Cholesterol is an essential component of cell membranes and serves as an important precursor of steroidal hormones and bile acids, but elevated levels of cholesterol and its oxidation products have been accepted as a risk factor for maintenance of health. The free and ester forms of cholesterol and fatty acids are the two major biological lipids. The aim of this hypothesis paper is to address the long-standing dogma that cholesterol is less susceptible to free radical peroxidation than polyunsaturated fatty acids (PUFAs). It has been observed that cholesterol is peroxidized much slower than PUFAs in plasma but that, contrary to expectations from chemical reactivity toward peroxyl radicals, cholesterol appears to be more readily autoxidized than linoleates in cell membranes. The levels of oxidation products of cholesterol and linoleates observed in humans support this notion. It is speculated that this discrepancy is ascribed to the fact that cholesterol and phospholipids bearing PUFAs are localized apart in raft and non-raft domains of cell membranes respectively and that the antioxidant vitamin E distributed predominantly in the non-raft domains cannot suppress the oxidation of cholesterol lying in raft domains which are relatively deficient in antioxidant.

Differences in Absorption and Metabolism between Structured 1,3-Oleate-2-palmitate Glycerol and 1-Oleate-2-palmitate-3-linoleate Glycerol on C57BL/6J Mice.

This study investigated differences in absorption and metabolism between 1,3-oleate-2-palmitate glycerol (OPO) and 1-oleate-2-palmitate-3-linoleate glycerol (OPL) using C57BL/6J mice. OPL was associated with higher postprandial plasma total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) concentrations, and the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C) compared to those of OPO (p > 0.05). OPO significantly increased postprandial oleic acid (OA) concentrations compared to OPL over the entire monitoring period (p < 0.05), while OPL significantly elevated linoleic acid (LA) levels compared to OPO (p < 0.05). After 1 month of feeding, the mice in both OPO and OPL groups showed lower final weight, weight gain, and liver TG, LDL-C, and LDL/HDL concentrations compared to the control (soybean oil) group. Lipidomics results showed that OPO increased the biosynthesis of very long-chain fatty acids and decreased the abundance of AcCa (16:1), AcCa (18:2), AcCa (18:1), AcCa (16:0), CarE (16:0), and CarE (16:1) relative to OPL. These lipid metabolites were positively correlated with liver TG, LDL-C, and LDL/HDL levels and negatively related to peroxisome proliferator-activated receptors α (PPARα) and acyl-CoA oxidase (ACOX1) expression. This study showed differences in physiologic functions between OPO and OPL and provided support for the future application of OPL in infant formula.

Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity.

Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.