Polyunsaturated Fatty Acid Esters Research Articles

Revisiting the Potential of Group VI Inorganic Precatalysts for the Ethenolysis of Fatty Acids through a Mechanochemical Approach.

The utilization of biobased feedstocks to prepare useful compounds is a pivotal trend in current chemical research. Among a varied portfolio of naturally available starting materials, fatty acids are abundant, versatile substrates with multiple applications. In this context, the ethenolysis of unsaturated fatty acid esters such as methyl oleate is an atom-economical way to prepare functional C10 olefins with a biobased footprint. Despite the existence of a variety of metathesis catalysts for the latter process, there is a lack of readily available, efficient, and inexpensive catalytic systems based on earth-abundant metals (Mo, W) whose preparation does not require sophisticated syntheses and manipulations. Here, a systematic exploration of homogeneous and heterogeneous inorganic Mo, W (oxy)halides shows that MoOCl4, while inactive as a homogeneous species, forms active and selective silica-supported ethenolysis precatalysts able to reach equilibrium conversion of methyl oleate within a few minutes upon activation with SnMe4. Such heterogeneous MoOCl4-based precatalysts were easily accessed through mechanochemical solvent-free procedures and found to contain, upon characterization by elemental analysis and Raman spectroscopy, isolated (≡SiO)Mo(=O)Cl3 units or polymeric silica-supported [-O(≡SiO)nMoCl4-nO-]m (n = 1, 2) complexes depending on the molybdenum loading. The former isolated species exhibited a higher catalytic performance. The developed heterogeneous precatalysts could be applied to the ethenolysis of various substrates, including polyunsaturated fatty acid esters and industrial fatty acid methyl ester (FAME) mixtures from palm oil transesterification.

The metabolic response of human trophoblasts derived from term placentas to metformin

Aims/hypothesisMetformin is increasingly used therapeutically during pregnancy worldwide, particularly in the treatment of gestational diabetes, which affects a substantial proportion of pregnant women globally. However, the impact on placental metabolism remains unclear. In view of the association between metformin use in pregnancy and decreased birthweight, it is essential to understand how metformin modulates the bioenergetic and anabolic functions of the placenta.MethodsA cohort of 55 placentas delivered by elective Caesarean section at term was collected from consenting participants. Trophoblasts were isolated from the placental samples and treated in vitro with clinically relevant doses of metformin (0.01 mmol/l or 0.1 mmol/l) or vehicle. Respiratory function was assayed using high-resolution respirometry to measure oxygen concentration and calculated {dot{V}mathrm{O}}_{2}. Glycolytic rate and glycolytic stress assays were performed using Agilent Seahorse XF assays. Fatty acid uptake and oxidation measurements were conducted using radioisotope-labelled assays. Lipidomic analysis was conducted using LC-MS. Gene expression and protein analysis were performed using RT-PCR and western blotting, respectively.ResultsComplex I-supported oxidative phosphorylation was lower in metformin-treated trophoblasts (0.01 mmol/l metformin, 61.7% of control, p<0.05; 0.1 mmol/l metformin, 43.1% of control, p<0.001). The proton efflux rate arising from glycolysis under physiological conditions was increased following metformin treatment, up to 23±5% above control conditions following treatment with 0.1 mmol/l metformin (p<0.01). There was a significant increase in triglyceride concentrations in trophoblasts treated with 0.1 mmol/l metformin (p<0.05), particularly those of esters of long-chain polyunsaturated fatty acids. Fatty acid oxidation was reduced by ~50% in trophoblasts treated with 0.1 mmol/l metformin compared with controls (p<0.001), with no difference in uptake between treatment groups.Conclusions/interpretationIn primary trophoblasts derived from term placentas metformin treatment caused a reduction in oxidative phosphorylation through partial inactivation of complex I and potentially by other mechanisms. Metformin-treated trophoblasts accumulate lipids, particularly long- and very-long-chain polyunsaturated fatty acids. Our findings raise clinically important questions about the balance of risk of metformin use during pregnancy, particularly in situations where the benefits are not clear-cut and alternative therapies are available.Graphical

137-OR: Metabolite Ratios and Development of Type 1 Diabetes

Ratios between metabolites more directly reflect flux through chemical reactions than individual metabolites. Variation in metabolites and their ratios are determined, in part, by genetic factors. Thus, genetic loci associated with variation in metabolite ratios may help disentangle genetic from non-genetic processes captured by the metabolome. We integrated metabolite ratios with genetics to predict changes preceding type 1 diabetes (T1D) in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Quantitative trait loci (QTLs) were identified for 132 metabolite ratios previously associated with progression from islet autoimmunity (IA) to T1D. Ratios were calculated from untargeted metabolomics data available at the time of seroconversion to IA for 338 cases and 921 matched controls in TEDDY. Genotyping was performed using a genome-wide array with custom content with imputation to the TOPMed reference panel. Ratio-SNP associations were estimated using Matrix eQTL software, adjusting for case-control status and genetic relatedness. Genome-wide significant association (P &amp;lt; 4.9×10-9) was observed at 202 independent loci, involving 49 metabolite ratios. Twenty-six loci (12.9%) involved ratios between polyunsaturated fatty-acids (PUFAs) and fatty acid esters of hydroxy fatty acids (FAHFAs), a novel class of bioactive lipids with antidiabetic and anti-inflammatory effects. Variation in the metabolite ratio of eicosadienoic acid to FAHFA (18:1/O-15:1) was significantly determined by a site on chromosome 3 (ITPR1); ITPR1 encodes a receptor integral to calcium signaling and glucose-induced insulin secretion. Other genetic loci contributing to variation of PUFA:FAHFA ratios reside in genes controlling inflammatory and innate immune response (e.g., TSPO, TTLL12, NCAM1) and apoptosis (PPM1L). These novel metabolite ratio QTLs, some with known association with T1D risk, expand potential biomarkers of T1D risk, with PUFA:FAHFA ratios representing candidate FAHFA biosynthesis genes. Disclosure R.K. Johnson: None. A. Romero: None. E. Willems: Employee; Amgen Inc. S.S. Rich: None. M. Rewers: Research Support; Provention Bio, Juvenile Diabetes Research Foundation (JDRF), Hemsley Charitable Trust, Dexcom, Inc., Janssen Research &amp; Development, LLC. O. Fiehn: None. J.M. Norris: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R03DK127472); National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; JDRF; Centers for Disease Control and Prevention

LPCAT3 Is Transcriptionally Regulated by YAP/ZEB/EP300 and Collaborates with ACSL4 and YAP to Determine Ferroptosis Sensitivity.

Aims: Lipid peroxidation occurring in lung adenocarcinoma (LUAD) cells leads to ferroptosis. Lysophosphatidylcholine acyl-transferase 3 (LPCAT3) plays a key role in providing raw materials for lipid peroxidation by promoting esterification of polyunsaturated fatty acids to phospholipids. Whether LPCAT3 determines ferroptosis sensitivity and the mechanism by which its expression is regulated in LUAD has not been reported. Results: LPCAT3 and acyl-coenzyme A (CoA) synthetase long-chain family member (ACSL)4 levels were positively associated with ferroptosis sensitivity in LUAD cell lines. Overexpression of LPCAT3 and ACSL4 sensitized LUAD cells to ferroptosis, while LPCAT3 and ACSL4 knockout showed the opposite effect. Zinc-finger E-box-binding (ZEB) was shown to directly bind the LPCAT3 promoter to stimulate its transcription in a Yes-associated protein (YAP)-dependent manner. An interaction between YAP and ZEB was also observed. E1A-binding protein p300 (EP300) simultaneously bound with YAP and ZEB, and induced H3K27Ac for LPCAT3 transcription. This mechanism was verified in primary LUAD cell and xenograft models. The ACSL4, LPCAT3, and YAP combination can jointly determine LUAD ferroptosis sensitivity. Innovation: The binding site of ZEB exists in the -1600 to -1401 nt region of LPCAT3 promoter, which promotes LPCAT3 transcription after ZEB binding. ZEB and YAP bind, and the ZEB zinc-finger cluster domain and YAP WW domain are crucial for their binding. EP300 may bind with YAP via its Bromo domain and with ZEB via its CBP/p300-HAT domain. In addition, the combination of ACSL4, LPCAT3, and YAP to determine ferroptosis sensitivity of LUAD cells is better than prostaglandin-endoperoxide synthase 2 (PTGS2), transferrin receptor (TFRC), or NADPH oxidase 1 (NOX1). Conclusion: LPCAT3 transcription is regulated by YAP, ZEB, and EP300. LUAD ferroptosis sensitivity can be determined by the combination of ACSL4, LPCAT3, and YAP. Antioxid. Redox Signal. 39, 491-511.

Abstract 12949: Altered Fatty Acids and Oxylipins Metabolism Differentiate Isolated Post-Capillary versus Combined Pre- and Post-Capillary Pulmonary Hypertension

Introduction: Pulmonary hypertension due to left heart disease (Group 2) is the most common type of pulmonary hypertension and has two subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the molecular characteristics that distinguish these two subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH), as has previously been suggested. Many lipid metabolites, including a diverse group of bioactive lipid mediators known as oxylipins, have been associated with cardiovascular disease and other inflammatory conditions. Therefore, we sought to characterize oxylipin and other bioactive lipid profiles among patients with Ipc-PH and Cpc-PH, as well as those with PAH. Methods: We studied 129 patients with Ipc-PH (n=38), Cpc-PH (n=52), or PAH (n=39) between June 2006 and March 2012. Liquid chromatography-mass spectrometry was used to assess 350 lipid metabolite analytes in each patient. Results: In multivariable analyses adjusting for age, sex, BMI, and pulmonary hypertension medications, we observed 34 metabolites were significantly increased and 10 were decreased in Ipc-PH compared to Cpc-PH (Figure). Among these same metabolites, only 9 were significantly different between Cpc-PH and PAH. Compared to patients with Ipc-PH, those with Cpc-PH had elevated levels of fatty acyl esters of hydroxy fatty acids and polyunsaturated fatty acids as well as lower levels of anti-inflammatory and pulmonary vascular relaxant oxylipins. Conclusions: Overall, these findings suggest that Cpc-PH may diverge from Ipc-PH and share some molecular similarities with PAH. Identifying key molecular targets involved in Cpc-PH pathophysiology may be critical for diagnostic purposes and in the development of novel therapeutic avenues for patients with Cpc-PH.

Biophysical modeling indicates a high affinity of ethyl esters of omega-3 polyunsaturated fatty acids to the enzymes of the pro-inflammatory arachidonic acid cascade

Background. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are widely used in modern cardiology. The anti-inflammatory effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is realized, in particular, by modulating the activity of the arachidonic acid (ARA) cascade.Objective: to conduct biophysical analysis of the interactions of various forms of PUFAs (ARA, EPA, DHA, EPA and DHA ethyl esters) with three target proteins-enzymes of the ARA cascade (cyclooxygenase-1 (COX-1), COX-2, 5-lipoxygenase (5-LPOG)).Material and methods. The minimization of the energy of the ligand-receptor complexes at various initial positions of the molecule relative to the receptor pocket and the molecular energy profiles of the protein (the energy of side chain transfer from solvent to protein) were calculated using the ECMMS package.Results. EPA and DHA ethyl esters were characterized by significantly higher absolute values of specific binding energies of target proteins than ARA or simply EPA/DHA. For example, in the case of COX-2, EPA, DHA and EPA ethyl ester had similar ∆∆G values (–3.0...–3.1 kcal/mol), while the COX-2 complex with DHA ethyl ester was somewhat more stable (∆∆G = –3.4 kcal/mol). In the case of the 5-LPOG enzyme, the complex with EPA ethyl ester was the most stable (∆∆G = –1.62 kcal/mol). Higher absolute binding energies indicate a higher affinity of EPA and DHA ethyl esters to enzymes of the ARA cascade.Conclusion. The results suggest that the high affinity of EPA and DHA ethyl esters to the enzymes of the ARA cascade is one of the molecular bases of therapeutic efficacy of ω-3 PUFAs with high degree of standardization.

Development of certified reference materials for four polyunsaturated fatty acid esters

Certified reference materials (CRMs) with high accuracy and traceability are essential tools for the validation of analytical methods and calibration of equipment. In this study, purity CRMs for four polyunsaturated fatty acids (PUFAs) esters, namely, cis-(4,7,10,13,16,19)- Docosahexaenoic acid methyl ester (DHA-ME), cis-4,7,10,13,16,19- Docosahexaenoic acid ethyl ester (DHA-EE), cis-(5,8,11,14,17)- Eicosapentaenoic acid methyl ester (EPA-ME) and cis-(5,8,11,14,17)- Eicosapentaenoic acid ethyl ester (EPA-EE), were first developed according to the ISO Guide. The CRMs’ purity values were assigned based on the average of quantitative nuclear magnetic resonance and mass balance approaches. The certified value with expanded uncertainties (k = 2, 95% confidence interval) were determined to be (98.8 ± 0.4) %, (99.0 ± 0.3) %, (98.9 ± 0.4) % and (98.9 ± 0.4) % for DHA-ME, DHA-EE, EPA-ME and EPA-EE, respectively. The four PUFAs esters were homogeneous and stable for 12 months at −4 °C and 7 days at 50 °C.

Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial

IntroductionThe lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥18 years) who had elevated baseline fasting serum triglycerides (TG).MethodsPatients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥500 and <1000 mg/dL or moderate HTG, with baseline TG >200 and <500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019).ResultsThe mean TG end-of-treatment effect of OM3EE was –29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were –12.12% and –23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience.DiscussionThese data indicate that OMACOR therapy at a dose of 2–4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated.

Prospects for biodiesel production from Macrotermes nigeriensis: Process optimization and characterization of biodiesel properties

The use of insects as feedstock for biodiesel production has sparsely been studied and very little is known of the fuel properties and engine performance of insect biodiesel. In this study, biodiesel was initially produced from an insect feedstock M. nigeriensis, then its physicochemical properties were characterized. The biodiesel was produced via the three-step process of lipid extraction, acid esterification (1 wt% H2SO4) and alkaline transesterification (0.5 wt% NaOH). The optimal reaction time, temperature and methanol-oil molar ratio for the acid-esterification process resulted in a free fatty acid conversion of 96.58%. The volumetric yield, fatty acid methyl esters content and physicochemical properties of M. nigeriensis biodiesel were analyzed using various analytical equipment such as the GC-HRMS, and 1H NMR. Analysis of the production process showed that 86.54 vol% biodiesel was obtained from M. nigeriensis oil. Further analysis showed that the biodiesel contained 96.72% fatty acid methyl esters. The composition of the fatty acid methyl esters was found to be 48% saturated esters and 52% monosaturated esters. The biodiesel density (841 kg m−3), viscosity (2.32 mm2 s−1), flash point (125 °C), pour point (−15 °C), cetane number (51.4), higher heating value (41.8 MJ kg−1) and acid value (0.44 mgKOH.g−1) were in compliance with the ASTM D6751 standards. One of the important results to highlight is the remarkably low viscosity of the biodiesel, which is attributed to the high concentration of monounsaturated fatty acid methyl esters. Lower viscosity of fuel helps to improve fuel atomization and combustion efficiency, and hence lower emissions. The absence of polyunsaturated fatty acid esters also indicates that the biodiesel will have good oxidation stability.

Influence of Omega-3 PUFA on Non-invasive factors determining the risk of arrhYthmias eXcess and sudden cardiac death in patients with HFpEF with ischemic etiology (ONYX)

Aim Patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) who have had acute myocardial infarction have an unfavorable prognosis, largely due to ventricular arrhythmias (VA) and risk of sudden cardiac death (SCD). The optimal treatment (triple neurohormonal blockade plus implantable cardioverter defibrillator and cardiac resynchronization therapy) reduced the risk of SCD primarily due to reverse cardiac remodeling, but has not solved this problem completely. Efficacy of purified ω-3 polyunsaturated fatty acid esters (PUFA) in low doses (1 g/day) in reducing VA and risk of SCD in HFrEF patients was demonstrated in two large randomized clinical trials. The PUFA effects was suggested to be related also with increased heart rhythm variability (HRV) and chronotropic action, which might depend on the drug dose. The present open, prospective, randomized, comparative study in parallel groups evaluated the effect of Omacor in different doses on noninvasive markers of SCD risk in patients with ischemic HFrEF receiving the optimal drug therapy.Methods Patients (n=40) were randomized at a 1:1:2 ratio to the control group (n=10), the Omacor 1 g/day treatment group (n=10), and the Omacor 2 g/day treatment group (n=20) and were followed up for 12 months. Clinical evaluation included changes in the CHF functional class (FC) and Clinical Condition Scale (CCS) score; concentration of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP); and peak oxygen consumption during exercise (peak VO2). The LV function was evaluated by LVEF. Holter ECG monitoring was used for evaluation of HRV (SDNN), average 24-h heart rate (HR), number of ventricular extrasystoles (VE) per hour and severity of VA, and presence of paired VE and VT runs.Results Improvement of CHF FC became significant only with the high-dose Omacor treatment (2 g/day). The CCS score showed a tendency towards decrease also with a lower dose (1 g/day) whereas the level of NT-proBNP significantly decreased with both Omacor doses. The increase in LV EF was significant only with the use of Omacor 2 g/day (+3 %, р=0.002). A negative chronotropic effect of ω-3 PUFA was observed. Average 24-h HR decreased by 8 bpm (р=0.05) and 11 bpm (р&lt;0.001) with Omacor 1 g/day and 2 g/day, respectively. Either dose of ω-3 PUFA significantly improved VO2, which directly correlated with LV EF and inversely correlated with HR. The decrease in number of VE was associated not only with improved HRV (SDNN) but also with the decrease in 24-h HR, and thus Omacor 2 g/day significantly decreased the number of VE (by 16 per hour) and dangerous VA (paired VE and VT runs ceased to be detected in 40 % of patients).Conclusion Since HR, HRV, and VA are closely interrelated, the effect of ω-3 PUFA specifically on these noninvasive markers apparently determines its ability to decrease the risk of SCD in patients with ischemic HFrEF. The antiarrhythmic effect of Omacor was greater with higher doses of this drug.

Azacarbazole n-3 and n-6 polyunsaturated fatty acids ethyl esters nanoemulsion with enhanced efficacy against Plasmodium falciparum

Alternative therapies are necessary for the treatment of malaria due to emerging drug resistance. However, many promising antimalarial compounds have poor water solubility and suffer from the lack of suitable delivery systems, which seriously limits their activity. To address this problem, we synthesized a series of azacarbazoles that were evaluated for antimalarial activity against D10 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains of P. falciparum. The most active compound, 9H-3-azacarbazole (3), was encapsulated in a novel o/w nanoemulsion consisting of ethyl esters of polyunsaturated fatty acids n-3 and n-6 obtained from flax oil as the oil phase, Smix (Tween 80 and Transcutol HP) and water. This formulation was further analyzed using transmission electron microscopy, dynamic light scattering and in vitro and in vivo studies. It was shown that droplets of the 3-loaded nanosystem were spherical, with satisfactory stability, without cytotoxicity towards fibroblasts and intestinal cell lines at concentrations corresponding to twice the IC50 for P. falciparum. Moreover, the nanoemulsion with this type of oil phase was internalized by Caco-2 cells. Additionally, pharmacokinetics demonstrated rapid absorption of compound 3 (tmax = 5.0 min) after intragastric administration of 3-encapsulated nanoemulsion at a dose of 0.02 mg/kg in mice, with penetration of compound 3 to deep compartments. The 3-encapsulated nanoemulsion was found to be 2.8 and 4.2 times more effective in inhibiting the D10 and W2 strains of the parasite, respectively, compared to non-encapsulated 3. Our findings support a role for novel o/w nanoemulsions as delivery vehicles for antimalarial drugs.

A novel process for the coproduction of biojet fuel and high-value polyunsaturated fatty acid esters from heterotrophic microalgae Schizochytrium sp. ABC101

Herein we demonstrated an economically beneficial process coproducing biojet fuel and high-value polyunsaturated fatty acids (PUFAs) from Schizochytrium sp. ABC101 microalgae. Schizochytrium is a promising biofuel source for its rapid growth, high cell density, and fast lipid accumulation via heterotrophic cultivation. The most important feature of Schizochytrium is that half of its lipids are composed of omega-3 PUFAs (i.e., docosahexaenoic acid and docosapentaenoic acid), which are currently commercialized as dietary supplements at a high price. We observed direct injection of PUFA-rich lipid into a high-temperature catalytic reactor can cause rapid catalyst deactivation via coke deposition. Therefore, the PUFAs were separated by short-path distillation after transesterification. The remaining esters of saturated fatty acids (SFAs) were catalytically deoxygenated into C13–C18n-paraffins, and then subsequently hydrocracked to produce iso-rich paraffins that are suitable as biojet fuel. As the result, 54.6 wt% PUFA-enriched esters (purity: 87.7%) and 20.4 wt% of qualified biojet fuel with respect to the initial lipids were obtained.

Antioxidant activity of highly hydroxylated fullerene C60 and its interactions with the analogue of α-tocopherol

Polyhydroxylated fullerenes (fullerenols) are excellent free radical scavengers. Despite the large number of reports on their reactions with reactive oxygen species, there is no report on their ability to trap lipid peroxyl radicals and act as chain-breaking antioxidants. In this work we studied the effect of fullerenol C60(OH)36 on the kinetics of peroxidation of polyunsaturated fatty acid ester (methyl linoleate) dispersed in two model systems that mimic biological systems: Triton X-100 micelles and Large Unilamellar Vesicles, at pH 4, 7 and 10. As a control antioxidant 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC, an analog of α-tocopherol) was used. In micellar systems at pH 4.0, C60(OH)36 reacts with peroxyl radicals with kinh= (5.8 ± 0.3) × 103 M−1s−1 (for PMHC kinh = 22 × 103 M−1s−1). Surprisingly, at pH 7 a retardation instead of inhibition was recorded, and at pH 10 no effect on the kinetics of the process was observed. In liposomal systems fullerenol was not active at pH 4.0 but at pH 7.0 kinh = (8.8 ± 2.6) × 103 M−1s−1 for fullerenol was 30% lower than kinh for PMHC. Using two fluorescent probes we confirmed that at pH 7.4 fullerenol/fullerenol anions are incorporated into the phospholipid heads of the bilayer. We also studied the cooperation of C60(OH)36 with PMHC: both compounds seem to contribute their peroxyl radical trapping abilities independently at pH 4 whereas at pH 7 and 10 a hyper-synergy was observed. The antioxidant action of C60(OH)36 and its synergy with PMHC was also confirmed for peroxidation of human erythrocytes at pH 7.4. Assuming the simplified structural model of fullerenol limited to 36 hydroxyls as the only functional groups attached to C60 core we found by density-functional theory a low energy structure with OH groups distributed in the form of two polyhydroxyl regions separating two unsubstituted carbon regions with biphenyl-like structure. Our calculations indicate that abstraction of hydrogen atom from fullerenol by peroxyl or tocopheroxyl radical is endoergic. As the electron transfer from fullerenol polyanion to the radicals is also energetically disfavoured, the most probable mechanism of reaction with radicals is subsequent addition of peroxyl/tocopheroxyl radicals to biphenyl moieties surrounded by OH groups.

Extraction of polyunsaturated fatty acids to reduce the iodine number of biodiesel products

In the last ten years, Indonesia has succeeded in realizing the production and commercialization of oxygenated biofuel/bioethanol and bioethanol, even has applied mixing biodiesel into diesel to up to 20%-volume (or known as a B20 mixture). This success has at least helped reduce imports of fuel oil (BBM) such as diesel and gasoline, but no more than 20%. The rest (i.e., at least 80%) must still be imported and will cause severe pressure on the country’s balance of payments because the current volume of fuel imports is no less than 50% of domestic needs. The quality of Indonesian biodiesel products generally still has a high cloud point and low oxidation stability. Diesel engine fuel consists of a mixture of methyl ester fatty acids (FAME: Fatty Acids Methyl Ester). Many constituent components are limited or not large (consist of 7-14 carbons). The essential constituents are the methyl esters of lauric, myristic, palmitic, stearic, oleic, linoleic, and linolenic acids. Methyl esters of polyunsaturated fatty acids (linoleic, linolenic, eleostearic) are inferior because they have a low cetane number and low oxidative stability. While methyl esters of saturated fatty acids have a superior demonic rate but have a high melting point (bad, higher than the requirements given by SNI). Related to the amount of unsaturated fat in biodiesel, it can reduce the quality of biodiesel, such as acid numbers, moisture content, and the emergence of sludge. Based on the current condition of biodiesel quality, to improve the quality of biodiesel produced can be done by reducing the number of unsaturated fats present in the biodiesel product. The initial step that has to be done is separation biodiesel products into saturated biodiesel with the characteristic iodine number <30-40 and unsaturated biodiesel with an iodine number > 70 through a fractionation process. Extraction was carried out using AgNO3 with variations in the ratio of biodiesel feed to solvents. The best ratio of biodiesel:AgNO3 to eliminate the levels of polyunsaturated free fatty acids in biodiesel products is 1:2 with an iodine value of 47.38 gr I2/(100 gr oil)

Calanus oil in the treatment of obesity-related low-grade inflammation, insulin resistance, and atherosclerosis.

Calanus oil (COil) is a natural product extracted from marine zooplankton Calanus finmarchicus found in the North Atlantic Ocean. This oil is rich in wax esters of polyunsaturated fatty acids (PUFAs) and has been projected as the best alternative to fish oil because its production cannot keep pace with the demands from the growing markets. The COil is the only commercially available marine source of wax esters, whereas classic ω-3 PUFAs comes from triglycerides, ethyl esters, and phospholipids. It has, in recent decades, been seen that there is an unprecedented rise in the use of PUFA-rich oil in the aquaculture industry. A simultaneous rise in the demand of PUFAs is also observed in the health care industry, where PUFAs are suggested preventing various disorders related to lifestyles such as obesity, diabetes mellitus, chronic low-grade inflammation, atherosclerosis, and brain and cardiovascular disorders (CVDs). In this review, we will explore the metabolic aspects related to the use of COil as an antioxidant, anticholesterinemic, and anti-inflammatory dietary source and its impact on the prevention and therapy of obesity-related metabolic disorders.

Effect of winterization and plant phenolic-additives on the cold-flow properties and oxidative stability of Karanja biodiesel

Poor stability and low-temperature operability are among the major hurdles in the commercialization of biodiesel. The presence of polyunsaturated fatty acid esters renders the fuel susceptible to oxidative attack while the long-chain saturated components limit its utility under low-temperature conditions. In this study, an attempt was made to improve these properties of Karanja biodiesel. Karanja biodiesel synthesized via a two-step alkali-catalyzed process exhibited poor stability and cold-flow properties. Karanja biodiesel was winterized to limit the content of long-chain saturates, and it had a favorable effect on the cloud and pour point of the fuel. Removal of long-chain saturated components led to an enrichment of the fuel in unsaturated fractions, and as a result, the stability of the fuel further deteriorated. For improving, the stability of the fuel T. cordifolia stem extract rich in phenolic constituents was added to winterized biodiesel. The combined treatment of winterization and phenolic-rich extract (1000 ppm) had a pronounced effect on fuel quality as it led to a reduction in the cloud (by 7 °C) and pour point (by 6 °C) and substantially improved the stability of the fuel under accelerated oxidative test conditions. The ASTM D6751, IS 15607, and EN 14214 specifications for the minimum induction period for blendstock biodiesel were satisfied. Thus, coupling the use of winterization and natural antioxidants offers novel opportunities in improving the fuel properties and acceptability of biodiesel in an efficient, economical, and environment-friendly manner.

Effect of Smoking Methods and Natural Spices on Quality and Consumer Acceptance of Smoked Silver Catfish (Chrysichthys nigrodigitatus).

Fish serves as a good source of dietary protein which is very inexpensive in relation to other animal protein foods and it is an excellent component of human diet. This study assessed the effects of smoking methods and natural spices on studied parameters and consumer acceptance of smoked silver catfish (Chrysichthys nigrodigitatus). One hundred samples of silver catfish were obtained by purposive sampling method. The fresh fish samples were smoked in two batches, the first batch was smoked with drum smoker and the second batch with oven smoker while the control was smoked without the natural spices. Rancidity indices (TVB-N, TMA-N, TBA and pH), microbiological analysis and sensory evaluation were carried out on smoked fish samples. The recent patents on edible fat blends (US20020031595A1), long chain fatty acids (WO2008085840A2) and esters of polyunsaturated fatty acids (US20090023808A1) helped in selecting the analytical methods. The results showed that there was statistical significant difference (P≤0.05) between total volatile base-nitrogen, trimethylamine values and pH of the smoked silver catfish samples treated with different concentrations of clove, ginger and garlic paste and those samples which were not treated with clove, ginger and garlic. This study showed that smoking methods has effects on quality indices, microbial quality and consumer acceptance of smoked silver catfish. Clove, ginger and garlic have some anti-oxidative effects on rancidity indices of smoked silver catfish as there was inverse relationship between clove, ginger and garlic and values of peroxide, free fatty acid and thiobarbituric acid. This was also observed for the microbial quality of the smoked silver catfish. There was also inverse relationship between clove, ginger and garlic and all the sensory parameters except for texture and as the concentrations of the natural spices increase the values of the sensory parameters decrease. In conclusion, this study showed that smoking methods affects the studied parameters, microbial quality and consumer acceptance of smoked silver catfish. Addition of clove, ginger and garlic had anti-microbial and anti-oxidative effects on quality parameters of smoked silver catfish. There was also a negative correlation between clove, ginger and garlic and all the sensory parameters except for texture.

Synthesis and Evaluation of Soy Fatty Acid Ester Estolides as Bioplasticizers in Poly(Vinyl Chloride)

AbstractPlasticizers are nonvolatile organic liquids that impart flexibility to polymers. Due to environmental, health, and safety reasons, the industry is looking for bioplasticizers to replace petroleum‐derived phthalates. To fulfill this need, soy fatty acid ester estolides were synthesized, characterized, and evaluated as phthalate replacements. Soybean oil was transesterified with methanol or glycerol to form lower molecular weight fatty acid esters that were epoxidized and ring opened with acetic acid and acetylated to give the final products. Ring opening and acetylation of the epoxidized oleic acid esters gave acyclic acetate fatty acid ester estolides, whereas the polyunsaturated fatty acid esters, linoleate, and linolenate gave cyclic tetrahydrofuran derivatives and cross‐linked higher molecular weight materials. The cyclization mechanism to form the tetrahydrofuran derivatives was postulated. Soy fatty acid ester estolides were compounded with formulated poly(vinyl chloride), (PVC) and tested for their functional properties. The physical and functional properties of the new bioplasticizers were compared with commercial plasticizers. The elasticity of PVC compounded with experimental plasticizers and commercial phthalates was comparable. PVC compounded with fatty acid methyl ester estolide showed lower glass transition temperature and similar tensile properties compared to PVC compounded with the commercial phthalate. PVC compounded with the glyceryl fatty acid ester estolide showed a higher glass transition temperature, higher tensile properties compared to PVC compounded with the commercial phthalate.

Tissue-Specific Ablation of ACSL4 Results in Disturbed Steroidogenesis.

ACSL4 is a member of the ACSL family that catalyzes the conversion of long-chain fatty acids to acyl-coenzyme As, which are essential for fatty-acid incorporation and utilization in diverse metabolic pathways, including cholesteryl ester synthesis. Steroidogenic tissues such as the adrenal gland are particularly enriched in cholesteryl esters of long-chain polyunsaturated fatty acids, which constitute an important pool supplying cholesterol for steroid synthesis. The current studies addressed whether ACSL4 is required for normal steroidogenesis. CYP11A1 promoter‒mediated Cre was used to generate steroid tissue‒specific ACSL4 knockout (KO) mice. Results demonstrated that ACSL4 plays an important role in adrenal cholesteryl ester formation, as well as in determining the fatty acyl composition of adrenal cholesteryl esters, with ACSL4 deficiency leading to reductions in cholesteryl ester storage and alterations in cholesteryl ester composition. Statistically significant reductions in corticosterone and testosterone production, but not progesterone production, were observed in vivo, and these deficits were accentuated in ex vivo and in vitro studies of isolated steroid tissues and cells from ACSL4-deficient mice. However, these effects on steroid production appear to be due to reductions in cholesteryl ester stores rather than disturbances in signaling pathways. We conclude that ACSL4 is dispensable for normal steroidogenesis.

Biomass production by Yarrowia lipolytica yeast using waste derived from the production of ethyl esters of polyunsaturated fatty acids of flaxseed oil

In recent years, in concern for human health, a dynamic growth in the production of ethyl esters of flexeed oil was observed. However the main by-product generated in the manufacture of esters is the glycerol fraction contains raw glycerol and polyunsaturated fatty acids. The presented study was aimed to produce biomass of Yarrowia lipolytica yeast using waste derived from the production of ethyl esters of polyunsaturated fatty acids of flaxseed oil.Yeast were screened for biomass production capability in 7-day shake-flask cultures (10 strains). The 7 selected strains were then cultivated for 12 h in a bioreactor in the medium containing a glycerol fraction (25 g/L). Based on results of the statistical analysis, Y. lipolytica S6 strain was selected for further experiments in a bioreactor. Submerged cultures were run in the production medium containing 25 and 40 g/L of glycerol fraction, fatty acids raw and pure glycerol. In the medium containing raw glycerol, strain S6 produced 21.3 g/L of biomass with the total yield of 0.51 g/g and productivity of 1.33 g/Lh. The yeast biomass contained from 19.4 to 48.2% of protein and from 7.38 to 30.51% of intra-cellular lipids.