Encapsulation of Docosahexaenoic Acid Oil Substantially Improves the Oxylipin Profile of Rat Tissues

Docosahexaenoic acid (DHA) is a major n-3 polyunsaturated fatty acid (PUFA) particularly involved in cognitive and cardiovascular functions. Due to the high unsaturation index, its dietary intake form has been considered to improve oxidation status and to favor bioaccessibility and bioavailability as well. This study aimed at investigating the effect of DHA encapsulated with natural whey protein. DHA was dietary provided as triacylglycerols to achieve 2.3% over total fatty acids. It was daily supplied to weanling rats for four weeks in omelet as food matrix, consecutively to a 6-hour fasting. First, when DHA oil was encapsulated, consumption of chow diet was enhanced leading to promote animal growth. Second, the brain exhibited a high accretion of 22.8% DHA, which was not improved by dietary supplementation of DHA. Encapsulation of DHA oil did not greatly affect the fatty acid proportions in tissues, but remarkably modified the profile of oxidized metabolites of fatty acids in plasma, heart, and even brain. Specific oxylipins derived from DHA were upgraded, such as Protectin Dx in heart and 14-HDoHE in brain, whereas those generated from n-6 PUFAs were mainly mitigated. This effect did not result from oxylipins measured in DHA oil since DHA and EPA derivatives were undetected after food processing. Collectively, these data suggested that dietary encapsulation of DHA oil triggered a more efficient absorption of DHA, the metabolism of which was enhanced more than its own accretion in our experimental conditions. Incorporating DHA oil in functional food may finally improve the global health status by generating precursors of protectins and maresins.

An Untargeted Lipidomic Analysis Reveals Depletion of Several Phospholipid Classes in Patients with Familial Hypercholesterolemia on Treatment with Evolocumab

Rationale: Familial hypercholesterolemia (FH) is caused by mutations in genes involved in low-density lipoprotein cholesterol (LDL-C) metabolism, including those for pro-protein convertase subtilisin/kexin type 9 (PCSK-9). The effect of PCSK-9 inhibition on the plasma lipidome has been poorly explored. Objective: Using an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, the plasma lipidome of FH subjects before and at different time intervals during treatment with the PCSK-9 inhibitor Evolocumab was explored. Methods and Results: In 25 FH subjects, heterozygotes or compound heterozygotes for different LDL receptor mutations, untargeted lipidomic revealed significant reductions in 26 lipid classes belonging to phosphatidylcholine (PC), sphingomyelin (SM), ceramide (CER), cholesteryl ester (CE), triacylglycerol (TG) and phosphatidylinositol (PI). Lipid changes were graded between baseline and 4- and 12-week treatment. At 12-week treatment, five polyunsaturated diacyl PC, accounting for 38.6 to 49.2% of total PC at baseline; two ether/vinyl ether forms; seven SM; five CER and glucosyl/galactosyl-ceramide (HEX-CER) were reduced, as was the unsaturation index of HEX-CER and lactosyl—CER (LAC-CER). Although non quantitative modifications were observed in phosphatidylethanolamine (PE) during treatment with Evolocumab, shorter and more saturated fatty acyl chains were documented. Conclusions: Depletion of several phospholipid classes occurs in plasma of FH patients during treatment with the PCSK-9 inhibitor Evolocumab. The mechanism underlying these changes likely involves the de novo synthesis of SM and CER through the activation of the key enzyme sphingomyelin synthase by oxidized LDL and argues for a multifaceted system leading to vascular improvement in users of PCSK-9 inhibitors.

Nutritional Indices for Assessing Fatty Acids: A Mini-Review

Dietary fats are generally fatty acids that may play positive or negative roles in the prevention and treatment of diseases. In nature, fatty acids occur in the form of mixtures of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA), so their nutritional and/or medicinal values must be determined. Herein, we do not consider the classic indices, such as ∑SFA, ∑MUFA, ∑PUFA, ∑n-6 PUFA, ∑n-3 PUFA, and n-6 PUFA/n-3 PUFA; instead, we summarize and review the definitions, implications, and applications of indices used in recent years, including the PUFA/SFA, index of atherogenicity (IA), the index of thrombogenicity (IT), the hypocholesterolemic/hypercholesterolemic ratio (HH), the health-promoting index (HPI), the unsaturation index (UI), the sum of eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA), fish lipid quality/flesh lipid quality (FLQ), the linoleic acid/α-linolenic acid (LA/ALA) ratio, and trans fatty acid (TFA). Of these nutritional indices, IA and IT are the most commonly used to assess the composition of fatty acids as they outline significant implications and provide clear evidence. EPA + DHA is commonly used to assess the nutritional quality of marine animal products. All indices have their advantages and disadvantages; hence, a rational choice of which to use is critical.

A detailed lipidomic study of human pathogenic fungi Candida auris

ABSTRACT The present study is an attempt to determine the lipid composition of Candida auris and to highlight if the changes in lipids can be correlated to high drug resistance encountered in C. auris. For this, the comparative lipidomics landscape between drug-susceptible (CBS10913T) and a resistant hospital isolate (NCCPF_470033) of C. auris was determined by employing high throughput mass spectrometry. All major groups of phosphoglycerides (PGL), sphingolipids, sterols, diacylglycerols (DAG) and triacylglycerols (TAG), were quantitated along with their molecular lipid species. Our analyses highlighted several key changes where the NCCPF_470033 showed an increase in PGL content, specifically phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine; odd chain containing lipids and accumulation of 16:1-DAG and 16:0-DAG; depletion of 18:1-TAG and 18:0-TAG. The landscape of molecular species displayed a distinct imprint between isolates. For example, the levels of unsaturated PGLs, contributed by both odd and even-chain fatty acyls were higher in resistant NCCPF_470033 isolate, resulting in a higher unsaturation index. Notwithstanding, several commonalities of lipid compositional changes between resistant C. auris and other Candida spp., the study could also identify distinguishable changes in specific lipid species in C. auris. Together, the data highlights the modulation of membrane lipid homeostasis associated with drug-resistant phenotype of C. auris.

Nutritional value of fatty acids of the Neotropical freshwater fishes Prochilodus magdalenae, Pseudoplatystoma magdaleniatum and Ageneiosus pardalis

This study aimed to determine the nutritional value of the fatty acids in the freshwater fish Prochilodus magdalenae, Pseudoplatystoma magdaleniatum and Ageneiosus pardalis during dry and wet Neotropical seasons with the view to generate useful information for nutrition and sustainable commercial exploitation. The analysis of fatty acids was performed by gas chromatography–mass spectrometry and the nutritional value was calculated using five estimators: n-6/n-3 ratio, unsaturation index (UI), atherogenicity index (AI), thrombogenicity index (TI) and ratio of hypocholesterolemic/hypercholesterolemic (h/H) fatty acids. A different number of fatty acids (P. magdaleniatum = 50, P. magdalenae = 41, and A. pardalis = 32) was identified for each species and the average abundance percentages were different in the two seasons (p < 0.05). Prochilodus magdalenae and P. magdaleniatum showed healthy n-6/n-3 ratios (1.04 and 2.72) in the different seasons. Although the three species showed low values of UI (0.37–0.63), the remaining nutritional indexes were within the healthy range (AI: 0.04–0.70, TI: 0.66–1.07, h/H: 0.80 – 24.40). Multivariate analysis showed similar healthy nutritional values for the species, with exception of P. magdaleniatum.

Concentration-Dependent Effects of N-3 Long-Chain Fatty Acids on Na,K-ATPase Activity in Human Endothelial Cells

N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0–20 μM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 μM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity.

FATTY ACID COMTENTS IN RAT ADIPOSE TISSUES UNDER ANAEROBIC EXERCISE AND HIGH-CALORIE DIETS

The objective of the paper is to study the effects of anaerobic exercise on fatty acids percentage in adipose tissues of different localization under high-calorie diets in rats. Materials and Methods. The authors examined Wistar rats under high calorie diets (32 % fat content). In the first group the animals were not exposed to any physical exercise. In the second group rats were exposed to anaerobic physical activity, namely swimming. The percentage of 24 fatty acids (FA) and the value of 14 integrative indicators (complexes) in the depot of visceral and subcutaneous adipose tissues were determined using chromatography-mass spectrometry (Agilent Technologies, USA). Results. Anaerobic exercise led to an increase in saturated FAs in the mesenteric adipose tissues and to a decrease in unsaturated FAs, as well as to a decrease in the unsaturation index; an increase in the retroperitoneal adipose tissue of the FA sphingophospholipid substrates, FA membrane substrates, a decrease in the energy substrates, an increase of vitamin F FA substrates due to ω6 of unsaturated FAs. At the same time, a decrease in the amount of polyunsaturated FAs was observed in the subcutaneous depot, and the balance between ω3/ω6 shifted towards ω6 of unsaturated FAs. In the mesenteric and retroperitoneal adipose tissues, there was a decrease in monounsaturated FAs due to ω9 of unsaturated FAs, and the ratio of saturated FAs/monounsaturated FAs shifted towards saturated FAs. Only in retroperitoneal adipose tissues there was a decrease in ω7 of saturated FAs due to C16: 1 ω7. Conclusion. Regular anaerobic exercise and a high-calorie diet showed the most pronounced effect on FAs in visceral adipose tissues, namely in mesenteric and retroperitoneal tissues. Keywords: fatty acids, fatty acid complexes, adipose tissues, anaerobic exercise, high-calorie diet. Цель – исследовать воздействие анаэробной физической нагрузки на процентное содержание жирных кислот в жировой ткани разной локализации на фоне питания повышенной калорийности у крыс. Материалы и методы. В исследовании использовали крыс линии Wistar, находящихся на питании повышенной калорийности (с долей жира 32 %). В первой группе животных физическая нагрузка отсутствовала, крысы второй группы получали физическую нагрузку преимущественно анаэробного характера в виде плавания. Процентное содержание 24 жирных кислот (ЖК) и значение 14 интегративных показателей (комплексов) в депо висцеральной и подкожной жировой ткани определяли на хромато-масс-спектрометре (Аgilent Technologies, США). Результаты. Анаэробная физическая нагрузка привела к увеличению содержания в мезентеральной жировой ткани насыщенных ЖК (НасЖК) и снижению ненасыщенных ЖК (НЖК), а также снижению индекса ненасыщенности; увеличению в забрюшинной жировой ткани ЖК-субстратов сфингофосфолипидов, ЖК-субстратов мембран, снижению субстратов энергии, увеличению содержания ЖК-субстратов витамина F за счет ω6 НЖК. При этом в подкожном депо наблюдалось снижение суммы полиненасыщенных ЖК, а баланс ω3/ω6 сместился в сторону ω6 НЖК. В мезентериальной и забрюшинной жировой ткани отмечалось снижение содержания мононенасыщенных ЖК (МНЖК) за счет ω9 НЖК, а соотношение НасЖК/МНЖК сместилось в сторону НасЖК. Только в забрюшинной жировой ткани было установлено снижение содержания ω7 НЖК за счет С16:1 ω7. Выводы. Регулярная анаэробная физическая нагрузка на фоне питания повышенной калорийности продемонстрировала наиболее выраженное влияние в отношении ЖК в висцеральной жировой ткани, а именно в мезентериальной и забрюшинной. Ключевые слова: жирные кислоты, комплексы жирных кислот, жировая ткань, анаэробная физическая нагрузка, диета повышенной калорийности.

EFFECT OF FATTY ACID BASED FUNCTIONAL LIPIDOMICS IN WOMEN WITH BREAST CANCER

Objective: Lipid metabolism alteration is a prominent feature during malignant transformation. We investigated the difference in plasma fatty acids (FAs) and molecular biomarkers in breast cancer women and controls. Methods: This comparative study was carried out on eighty breast cancer women and forty control women. FAs were analyzed in gas chromatography and calculated as a percentage of total FAs. FA molecular markers were estimated by the FA data. Non-parametric statistical tests were used. Results: Saturated FAs were higher in the case group. Control group had higher linoleic acid (p=0.04), suggesting decreased desaturase activity. N-6 FAs were higher and n-3 FAs were lower in breast cancer cases. The n6/n3 ratio, cardiovascular risk ratio (p<0.001), and inflammatory risk ratio were high, whereas saturation index and unsaturation index (p=0.05) were lower in breast cancer cases. Conclusion: Lipidomics of the cell membrane is significantly influenced by FAs, and the dietary FAs regulate the enzymatic activities in the FA metabolism pathway.

Mycorrhizas enhance drought tolerance of citrus by altering root fatty acid compositions and their saturation levels

Arbuscular mycorrhizas (AMs) have the ability to enhance drought tolerance of citrus, but the underlying mechanisms have not been clearly elucidated. Considering the strong association of cell membrane fatty acid (FA) unsaturation with plant drought tolerance, the present study hypothesized that AM fungi (AMF) modulated the composition and unsaturation of FAs to enhance drought tolerance of host plants. Drought-sensitive citrus rootstocks, trifoliate orange (Poncirus trifoliata) seedlings, were inoculated with AMF (Funneliformis mosseae) for 3 months and were subsequently exposed to drought stress (DS) for 8 weeks. Mycorrhizal seedlings exhibited better plant growth performance, higher leaf water potential and lower root abscisic acid concentrations under both well-watered (WW) and DS conditions. Arbuscular mycorrhiza fungus inoculation considerably increased root methyl oleate (C18:1), methyl linoleate (C18:2) and methyl linolenate (C18:3N3) concentrations under both WW and DS conditions, and root methyl palmitoleate (C16:1) concentrations under WW, while it decreased root methyl stearate (C18:0) levels under both WW and DS. These changes in the composition of FAs of mycorrhized roots resulted in higher unsaturation index of root FAs, which later aided in reducing the oxidative damage on account of lower concentration of malondialdehyde and superoxide radicals. The changes of these FAs were a result of AMF-up-regulating root FA desaturase 2 (PtFAD2), FA desaturase 6 (PtFAD6) and Δ9 FA desaturase (PtΔ9) genes under WW and PtFAD2, PtFAD6 and Δ15 FA desaturase (PtΔ15) genes under DS conditions. Our results confirmed that mycorrhization brought significant changes in root FA compositions, in addition to regulation of gene expression responsible for increasing the unsaturation level of FAs, a predisposing physiological event for better drought tolerance of citrus.