Stearidonic-Enriched Soybean Oil Modulates Obesity, Glucose Metabolism, and Fatty Acid Profiles Independently of Akkermansia muciniphila.

SCOPE: Previous studies have suggested that diets rich in omega-3 and low in omega-6 long-chain polyunsaturated fatty acids (PUFAs) can limit the development of metabolic syndrome (MetS). Transgenic soybeans yielding oils enriched for omega-3 PUFAs represent a new and readily-available option for incorporating omega-3 PUFAs into diets to provide health benefits. METHODS AND RESULTS: Transgenic soybean oils, enriched for either stearidonic acid (SDA) or eicosapentaenoic acid (EPA), are incorporated into diets to test their effects on limiting the development of MetS in a mouse model of diet-induced obesity. Supplementation with SDA- but not EPA-enriched oils improved features of MetS compared to feeding a control wild-type oil. Because previous studies have linked the gut microorganism Akkermansia muciniphila to the metabolic effects of feeding omega-3 PUFAs, the causal contribution of A. muciniphila to mediating the metabolic benefits provided by SDA-enriched diets is investigated. Although A. muciniphila is not required for SDA-induced metabolic improvements, this microorganism does modulate levels of saturated and mono-unsaturated fatty acids in host adipose tissues. CONCLUSION: Together, these findings support the utilization of SDA-enriched diets to modulate weight gain, glucose metabolism, and fatty acid profiles of liver and adipose tissue.

Bioavailable phytoprostanes and phytofurans from Gracilaria longissima have anti-inflammatory effects in endothelial cells.

BACKGROUND: An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae. Among them, phytoprostanes (PhytoPs) and phytofurans (PhytoFs), both autoxidation products of α-linolenic acid, have been seen to exert immunomodulatory and antiinflammatory activities in vitro. The purpose of this study was to explore the bioaccesibility, bioavailability, and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima, and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells. METHODS: The PhytoPs and PhytoFs profile and concentration of G. longissima were determined by UHPLC-QqQ-MS/MS. Algal samples were processed following a standardised digestion method including gastric, intestinal, and gastrointestinal digestion. The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier. The inflammation response of these prostaglandin-like compounds in human endothelial cells, after intestinal absorption, was investigated in vitro. RESULTS: Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42 µg per 100 g, respectively, on average, although permeability through the Caco-2 cell monolayer was high (up to 88.2 and 97.7%, on average, respectively). PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers. The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins, suggesting pro- or anti-inflammatory activity on their part. In this aspect, the cross-reactivity of these compounds with diverse receptors, and their relative concentration could explain the diversity of the effects found in the current study. CONCLUSIONS: The results indicate that PhytoPs and PhytoFs display complex pharmacological profiles probably mediated through their different actions and affinities in the endothelium.

Simulated in vitro infant gastrointestinal digestion of yak milk fat globules: A comparison with cow milk fat globules.

Lipolysis products released during digestion exert positive metabolic impacts on the nutrition of newborns. However, the lipolysis behavior of yak milk lipids during digestion remains unknown. In this study, the simulated in vitro infant gastrointestinal digestion of cow, yak and standardized yak milk fat globules the same size as those from cow milk (Cow MF, Yak MF and Yak SMF) were compared. Although Cow MF showed a higher lipolysis rate at the beginning of gastric digestion, Yak MF and Yak SMF exhibited a higher lipolysis level during later gastrointestinal digestion. Higher hydrolysis efficiency of yak milk lipids was due to their lipid properties, including their composition and structure. Furthermore, yak milk lipids released more unsaturated fatty acids than Cow MF throughout digestion. This study highlights the crucial role of lipid characteristics in the efficient digestion of milk lipids and provides new insight for the design of yak milk infant diets.

A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.

9cUAB30 is a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models. The purpose of this phase I placebo-controlled, double-blinded, dose escalation study of 9cUAB30 was to evaluate its safety, pharmacokinetics, and determine a dose for future phase II studies. Participants received a single dose of study drug (placebo or 9cUAB30) on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing starting on day 8. Fifty-three healthy volunteers were enrolled into five dose cohorts (20, 40, 80, 160, and 240 mg). Participants were randomized within each dose level to receive either 9cUAB30 (n = 8) or placebo (n = 2). 9cUAB30 was well tolerated, with no dose limiting toxicities reported and no evidence of persistent elevations in serum triglycerides or cholesterol. Treatment-emergent grade 3 hypertension occurred in 1 of 8 participants at the 20 mg dose level and in 2 of 8 at the 240 mg dose level, all considered unlikely related to study agent; no other grade 3 adverse events were observed. The AUC increased, as expected, between day 1 (single dose) and day 36 (steady state). Pharmacokinetics were linear in dose escalation through 160 mg. 9cUAB30 administered by daily oral dosing has a favorable safety and pharmacokinetic profile. On the basis of the observed safety profile and lack of linearity in pharmacokinetics at doses greater than 160 mg, the recommended phase II dose with the current formulation is 160 mg once daily.

Effects of nano-sizing on lipid bioaccessibility and ex vivo bioavailability from EPA-DHA rich oil in water nanoemulsion.

The physiological efficacy of nutraceuticals is dependent on their physicochemical nature and bioavailability across biological barriers. In the present work, effects of nano-sizing of emulsion-based delivery vehicle on the bioavailability of polyunsaturated fatty acids rich fish oil have been investigated via three-step experimental design; ex vivo rat everted intestinal sac model, cellular lipid uptake and the bioactivity in rat PBMCs. Nanoemulsion in comparison to the conventional emulsion has shown significant higher rate of uptake of polyunsaturated fatty acids in three segments of small intestine. The time-kinetics of such uptake was correlated with appearance of short-chain fatty acids in basal side of the everted sac. The bioavailability of the formulated fish oil and its inhibitory response against lipopolysaccharide-induced nitric oxide production in rat PBMCs were positively correlated. This formulation with nano-sized droplets can be utilized as smart delivery vehicles for designing oral therapies in future.

Fitness for purpose and stability assessment of long-chain polyunsaturated fatty acids in chicken tissues.

The global popularity of chicken in human diets make it an obvious choice for enrichment with DHA and LC-PUFA. There is presently a need for a robust method for the analysis of chicken tissues and where the fitness for purpose of the method has been demonstrated. The purpose of this paper is to present the validation of the AOAC method 996.06 on five different chicken tissues; breast, thigh, skin, kidney and liver. The parameters investigated as part of the validation study included; linearity and range, the limit of detection and limit of quantification, accuracy, repeatability, inter-analyst reproducibility, and specificity. The method was further applied to assess the stability of DHA and other specific LC-PUFA in chicken tissues over short and long timepoints. The disclosure of this information is relevant for researchers concerned with the analysis of LC-PUFA in regulatory and efficacy studies.

Cytotropic heterogeneous molecular lipids inhibit the growth of glioma cells by inducing apoptosis and autophagy.

The cytotropic heterogeneous molecular lipid (CHML) is a mixture of lipids isolated from natural products. CHML is an effective therapy for various kinds of cancers; however, the effect of CHML on glioma cells was seldom reported. Here, we aim to explore the cytotoxicity of CHML on glioma cells, and analyze the possible mechanisms. U251 glioma cells were cultured with CHML at different concentration, and the growth inhibition was measured by CCK-8 assay. Induced apoptosis were detected by flow cytometry, and the induced autophagies were observed by a transmission electron microscope. The key molecules involved in apoptosis and autophagy were detected by quantitative PCR and western-blot. CHML might inhibit the growth of U251 cells and promote apoptosis by up-regulating the expressions of Caspase-8 and Caspase-3; CHML also induced autophagy of U251 cells by promoting the expressions of MAP LC-3 and Beclin-1. CHML can inhibit proliferation of U251 cells by promoting cell apoptosis and inducing autophagy.

Designing Natural Product Hybrids Bearing Triple Antiplatelet Profile and Evaluating Their Human Plasma Stability.

Cardiovascular diseases (CVDs) are becoming major contributors to the burden of disease due to genetic and environmental factors. Despite current standard oral care, cardiovascular risk remains relatively high. A triple antiplatelet therapy with a cyclooxygenase-1 (COX-1) inhibitor, a P2Y12 receptor antagonist, and a protease-activated receptor-1 (PAR-1) antagonist has been established in the secondary prevention of atherothrombosis in patients with acute myocardial infraction and in those with peripheral artery disease. However, due to the combinatorial use of three different drugs, patients receiving this triple therapy are exposed to enhanced risk of bleeding. Conforming to polypharmacology principles, the discovery of a single compound that can simultaneously block the three platelet activation pathways (PAR-1, P2Y12, and COX-1) is of importance. Natural products have served as an inexhaustible source of bioactive compounds presenting a diverse pharmaceutical profile, including anti-inflammatory, antioxidant, anticancer, and antithrombotic activity. Indeed, principal component analysis indicated that natural products have the potential to inhibit the three aforementioned pathways, though existed reports refer to single inhibition mechanism on specific receptor(s) implicated in platelet activation. We thus set out to explore possibilities that take advantage of this potential of natural products and shape the basis to produce novel compounds that could simultaneously target PAR-1, P2Y12, and COX-1 platelet activation pathways. Polyunsaturated fatty acids (PUFAs) have multiple effects leading to improvements in blood pressure and cardiac function and arterial compliance. A promising approach to achieve the desirable goal is the bioconjugation of natural products with PUFAs. Herein, we describe the principles that should be followed to develop molecular hybrids bearing triple antiplatelet activity profile.

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins.

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA.

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers. They were run in the absence and presence of 20mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, S¯CD=0.152). EPA-PC (S¯CD=0.131) is most disordered, while DPA-PC (S¯CD=0.140) is least disordered. DHA-PC (S¯CD=0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (S¯CD=0.169), DHA-PC (S¯CD=0.178) and DPA-PC (S¯CD=0.182) is increased less than in OA-PC (S¯CD=0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy.

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.

Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS(2) method was used to quantify pellitorine. Results. Pellitorine was able to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the basolateral-to-apical side with apparent permeability coefficients between 0.6 · 10(-5) and 4.8 · 10(-5) cm/h and between 0.3 · 10(-5) and 5.8 · 10(-5) cm/h, respectively. In rats, a serum elimination rate constant of 0.3 h(-1) was obtained. Intravenous injection of pellitorine in mice resulted in a rapid and high permeation of pellitorine through the BBB with a unidirectional influx rate constant of 153 µL/(g·min). In particular, 97% of pellitorine reached the brain tissue, while only 3% remained in the brain capillaries. An efflux transfer constant of 0.05 min(-1) was obtained. Conclusion. Pellitorine shows a good gut permeation and rapidly permeates the BBB once in the blood, indicating a possible role in the treatment of central nervous system diseases.

Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi.

Bioavailability of long chain omega-3 polyunsaturated fatty acids from phospholipid-rich herring roe oil in men and women with mildly elevated triacylglycerols.

This randomized, single-blind, crossover trial assessed the bioavailability of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) from two different sources, each examined over a 12h period following consumption of a single serving and after 2-weeks of daily supplementation. Thirty-two adults with fasting triacylglycerol (TAG) concentrations between 100 and 399mg/dL were randomly assigned, with stratification by sex and age, to receive 12 capsules/day containing either phospholipid (PL)-rich herring roe oil (Romega® 30, 628mg/day EPA; 1810mg/day DHA; 137mg/day DPA) or TAG-rich fish oil (575mg/day EPA; 1843mg/day DHA; 259mg/day DPA) each for a 2-week period separated by a 4 week washout. The net incremental area under the curve from 0 to 12h for EPA, DHA, and EPA+DHA in plasma phosphatidylcholine (PC) were significantly higher (p<0.01 for all) after Romega 30 supplementation compared to fish oil. Similar results were observed when the data for the Romega 30 condition were normalized to fish oil EPA and DHA intakes (p<0.001 for all). After the 2-week supplementation period, fasting plasma PC EPA+ DHA was elevated by ~2.8 to 3.0-fold relative to baseline in both conditions (p<0.0001 for each), but there was no significant difference in the change from baseline (p=0.422) between Romega 30 (baseline=62.2±3.8µg/mL vs. end of study=172.9±11.7µg/mL) and fish oil (baseline=62.0±3.4µg/mL vs. end of study=185.4±11.2µg/mL) conditions. Similar results were observed for each individual LC n-3 PUFA in plasma PC after 2 weeks of supplementation. These data demonstrate that PL-rich herring roe is a well-tolerated and bioavailable source of LC n-3 PUFA.

A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.

Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay. Biotinylated leptomycin B (b-LMB) was utilized as a tool compound to measure SINE-free XPO1. Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo. Evaluation of a panel of selinexor sensitive and resistant cell lines revealed that resistance was not attributed to XPO1 occupancy by selinexor. Administration of a single dose of selinexor bound XPO1 for minimally 72 hours both in vitro and in vivo. While XPO1 inhibition directly correlates with selinexor pharmacokinetics, the biological outcome of this inhibition depends on modulation of pathways downstream of XPO1, which ultimately determines cancer cell responsiveness.

Protection of polyunsaturated fatty acids against ruminal biohydrogenation: Pilot experiments for three approaches.

Three methods for protection of PUFA against biohydrogenation by ruminal microorganisms were evaluated. In method 1 a blend of ground flaxseed, calcium oxide, and molasses was processed through a dry extruder. In method 2, a blend of ground flaxseed, soybean meal, molasses, and baker's yeast was moistened and prewarmed, allowing enzymes from yeast to produce reducing sugars, and the mixture was subsequently processed through a dry extruder like in method 1. In method 3, ground flaxseed was embedded within a matrix of dolomitic lime hydrate (L-Flaxseed) as a protective barrier against biohydrogenation. Dolomitic lime was mixed with ground flaxseed, water was added, the mixture was blended in a high-speed turbulizer, and the resulting material was then dried to form a granular matrix. Methods 1 and 2 were tested in 1 study (study 1), and method 3 was tested in 2 studies (studies 2 and 3). In study 1, 60 crossbred yearling steers (BW = 475 ± 55 kg) were used in a randomized complete block design experiment. Steers were fed for 12 d with a diet consisting of 48.73% steam-flaked corn, 35% wet corn gluten feed, 12% corn silage, and 4.27% vitamins and minerals (Control). For the other 4 treatments, a portion of wet corn gluten feed was replaced with 5% of unprocessed or extruded mixtures as described for methods 1 and 2. Steers were weighed, and jugular blood samples were taken for analysis of long-chain fatty acids (LCFA) on d 0 and 12 of the study. Both methods failed to improve resistance of PUFA against biohydrogenation (P > 0.1). In study 2, in situ fatty acid disappearance was evaluated for ground flaxseed (Flaxseed) or L-Flaxseed using 6 ruminally fistulated Holstein steers. The proportion of α-linolenic acid (ALA) that was resistant to ruminal biohydrogenation was approximately 2-fold greater for L-Flaxseed than for Flaxseed (P < 0.05). In study 3, 45 steers (269 ± 19.5 kg initial BW) were used in a randomized complete block design. Steers were fed diets containing 0% Flaxseed (No Flaxseed), and in treatments 2 and 3, a portion of flaked corn was replaced with Flaxseed or L-Flaxseed. Animals were weighed and blood samples were taken on d 0, 7, and 14 of the study, and LCFA were analyzed. The use of L-Flaxseed in study 3 increased plasma concentrations of ALA to more than 4 times the level observed in cattle fed unprotected flaxseed, suggesting the dolomitic lime hydrate was effective as a protective barrier against biohydrogenation.

Quantitative transdermal behavior of pellitorine from Anacyclus pyrethrum extract.

The plant Anacyclus pyrethrum (AP) consists of several N-alkylamides with pellitorine as main constituent. AP extracts are known to be biologically active and some products for topical administration containing AP plant extracts are already commercially available with functional cosmeceutical claims. However, no transdermal data for pellitorine are currently available. Therefore, our general goal was to investigate the local skin pharmacokinetics of the plant N-alkylamide pellitorine using a Franz diffusion cell set-up. Two different forms were applied on human skin: purified pellitorine and the AP extract. Our study demonstrated that pellitorine is able to cross the stratum corneum and the subsequent skin layers. A significantly higher permeability coefficient was observed when the AP extract (Kp=2.3 × 10(-4)cm/h) was administered, compared to purified pellitorine (Kp=1.1 × 10(-4)cm/h). With the obtained pellitorine concentrations in the skin layers and the receptor fluid, it is concluded that local and systemic effects can be expected after topical application. Due to these findings and as a regulatory consequence, products containing reasonable concentrations of pellitorine are recommended to be classified as a medicinal product.

The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population.

BACKGROUND: Ingestion of polyunsaturated fatty acids (PUFAs) has been proposed to influence several chronic diseases including coronary heart disease (CHD) and type-2 diabetes (T2D).There is strong evidence that omega-3 (n-3) PUFAs provide protection against CHD and biomarkers of atherosclerosis. In contrast, there is more limited and inconsistent data for T2D. Few studies have examined the impact of n-3 PUFA-containing botanical oils on T2D. METHODS: Fifty-nine subjects with early-stageT2D or metabolic syndrome participated in an 8-week, randomized, single-blind, parallel intervention study and were provided PUFA-containing oils. Individuals received either corn oil (CO), a botanical oil (BO) combination (borage [Borago officinalis L.]/echium oil [Echium plantagineum L.]) or fish oil (FO). The BO combination was enriched in alpha-linolenic, gamma-linolenic, and stearidonic acids and the FO in eicosapentaenoic and docosahexaenoic acids. Serum fatty acids and other serum lipids(triglycerides and total, HDL and LDL cholesterol), as well as markers of inflammation (leptin, and C-reactive protein) and glucose regulation (glucose and hemoglobin A1c) were assessed from fasting participants at baseline and after the intervention. RESULTS: Compliance was verified by expected increases in specific PUFAs in each of the three oil arms. Participants in the CO group showed no differences in serum lipids, markers of inflammation or glucose regulation between pre- and post-treatment measures. Supplementation with BO significantly lowered total and LDL cholesterol levels and FO reduced serum triglycerides, hemoglobin A1c and increased HDL-cholesterol. CONCLUSION: Short-term dietary supplementation with BO and FO improved biomarkers associated with T2D/metabolic syndrome. TRIAL REGISTRATION: Clinicaltrial.gov NCT01145066.

Enteral and parenteral lipid requirements of preterm infants.

Lipids provide infants with most of their energy needs. The major portion of the fat in human milk is found in the form of triglycerides, the phospholipids and cholesterol contributing for only a small proportion of the total fat. Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for normal development of the central nervous system and have potential for long-lasting effects that extend beyond the period of dietary insufficiency. Given the limited and highly variable formation of docosahexaenoic acid (DHA) from α-linolenic acid, and because DHA is critical for normal retinal and brain development in the human, DHA should be considered to be conditionally essential during early development. In early enteral studies, the amount of LC-PUFAs administered in formula was chosen to produce the same concentration of arachidonic acid and DHA as in term breast milk. Recent studies report outcome data in preterm infants fed formula with DHA content 2-3 times higher than the current concentration. Overall, these studies show that providing larger amounts of DHA supplements is associated with better neurological outcomes and may provide other health benefits. One study further suggests that the smallest babies are the most vulnerable to DHA deficiency and likely to reap the greatest benefit from high-dose DHA supplementation. Current nutritional management may not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods and in very preterm/very low birth weight infants until due date and higher amounts than those routinely used are likely to be necessary to compensate for intestinal malabsorption, DHA oxidation, and early deficit. Recommendations for the healthcare provider are made in order to prevent lipid and more specifically LC-PUFA deficit. Research should be continued to fill the gaps in knowledge and to further refine the adequate intake for each group of preterm infants.

Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.

OBJECTIVE: Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. APPROACH AND RESULTS: The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. CONCLUSIONS: Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.