Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.

AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS: In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS: SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION: Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION: ClinicalTrials.gov .NCT01736202. FUNDING: German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.

Safflower (Carthamus tinctorius L.) oil could improve abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated. AIM OF THE STUDY: The present study aimed to evaluate the effects of safflower oil on MetS risk factors. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities. RESULTS: Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p<0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes. CONCLUSION: Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.

Changes in the growth, ileal digestibility, intestinal histology, behavior, fatty acid composition of the breast muscles, and blood biochemical parameters of broiler chickens by dietary inclusion of safflower oil and vitamin C.

BACKGROUND: The effects of safflower oil and vitamin C (Vit. C) inclusion in broiler chicken diets on the growth performance, apparent ileal digestibility coefficient "AID%" of amino acids, intestinal histology, behavior, carcass traits, fatty acid composition of the breast muscle, antioxidant and immune status for a 35-day feeding period were evaluated. A total of 300 three-day-old Ross chicks (58.25 g ± 0.19) were randomly allotted in a 2 × 3 factorial design consisting of two levels of vitamin C (0 and 400 mg/kg diet) and three levels of safflower oil (0, 5, and 10 g/kg diet). RESULTS: An increase in the final body weight, total body weight gain, total feed intake, and the relative growth rate (P <  0.05) were reported by safflower oil and vitamin C inclusion. Dietary supplementation of safflower oil and vitamin C had a positive effect (P <  0.05) on the ingestive, resting, and feather preening behavior. Vitamin C supplementation increased (P <  0.05) the AID% of lysine, threonine, tryptophan, arginine, and valine. Safflower inclusion (10 g/kg) increased (P <  0.05) the AID% of methionine and isoleucine. Safflower oil inclusion increased (P <  0.05) the levels of stearic acid, linoleic acid, saturated fatty acids, and omega-3 fatty acids (ω-3) in the breast muscle. In contrast, the supplementation of only 10 g of safflower oil/kg diet increased (P = 0.01) the omega-3/omega-6 (ω-3/ω-6) fatty acids ratio. Vit. C supplementation increased (P <  0.05) the CAT serum levels, SOD, and GSH enzymes. Dietary supplementation of safflower oil and vitamin C improved the intestinal histology. They increased the villous height and width, crypt depth, villous height/crypt depth ratio, mucosal thickness, goblet cell count, and intra-epithelium lymphocytic lick cell infiltrations. The serum levels of IgA and complement C3 were increased (P <  0.01) by Vit. C supplementation and prominent in the 400 vit. C +  10 safflower Oil group. CONCLUSION: A dietary combination of safflower oil and vitamin C resulted in improved growth rate, amino acids AID%, intestinal histology, welfare, immune and antioxidant status of birds, and obtaining ω-3 and linoleic acid-enriched breast muscles. The best inclusion level was 400 vit. C +  10 safflower Oil.

Comparison of Dietary Oils with Different Polyunsaturated Fatty Acid n-3 and n-6 Content in the Rat Model of Cutaneous Wound Healing.

Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wound healing in the rat model. Rats were fed the feed mixture with 8% palm oil (P), safflower oil (S), fish oil (F) or Schizochytrium microalga extract (Sch) and compared to the animals fed by control feed mixture (C). Dorsal full-thickness cutaneous excisions were performed after 52 days of feeding and skin was left to heal for an additional 12 days. Histopathological analysis of skin wounds was performed, including immune cells immunolabeling and the determination of hydroxyproline amount as well as gene expression analyses of molecules contributing to different steps of the healing. Matrix-assisted-laser-desorption-ionization mass-spectrometry-imaging (MALDI-MSI) was used to determine the amount of collagen α-1(III) chain fragment in healing samples. Treatment by Schizochytrium extract resulted in decrease in the total wound area, in contrast to the safflower oil group where the size of the wound was larger when comparing to control animals. Diet with Schizochytrium extract and safflower oils displayed a tendency to increase the number of new vessels. The number of MPO-positive cells was diminished following any of oil treatment in comparison to the control, but their highest amount was found in animals with a fish oil diet. On the other hand, the number of CD68-positive macrophages was increased, with the most significant enhancement in the fish oil and safflower oil group. Hydroxyproline concentration was the highest in the safflower oil group but it was also enhanced in all other analyzed treatments in comparison to the control. MALDI-MSI signal intensity of a collagen III fragment decreased in the sequence C > S > Sch > P > F treatment. In conclusion, we observed differences in tissue response during healing between dietary oils, with the activation of inflammation observed following the treatment with oil containing high eicosapentaenoic acid (EPA) level (fish oil) and enhanced healing features were induced by the diet with high content of docosahexaenoic acid (DHA, Schizochytrium extract).

Effect of vegetable oils on the experimental infection of mice with Trypanosoma congolense.

Vegetable oils are frequently used as solvents for lipophilic materials; accordingly, the effects of their components should be considered in animal experiments. In this study, the effects of various vegetable oils on the course of Trypanosoma congolense infection were examined in mice. C57BL/6J mice were orally administered four kinds of oils (i.e., coconut oil, olive oil, high oleic safflower oil, and high linoleic safflower oil) with different fatty acid compositions and infected with T. congolense IL-3000. Oil-treated mice infected with T. congolense showed significantly higher survival rates and lower parasitemia than those of control mice. Notably, coconut oil, which mainly consists of saturated fatty acids, delayed the development of parasitemia at the early stage of infection. These results indicated that vegetable oil intake could affect T. congolense infection in mice. These findings have important practical implications; for example, they suggest the potential effectiveness of vegetable oils as a part of the regular animal diet for controlling tropical diseases and indicate that vegetable oils are not suitable solvents for studies of the efficacy of lipophilic agents against T. congolense.

Encapsulation of lipids as emulsion-alginate beads reduces food intake: a randomized placebo-controlled cross-over human trial in overweight adults.

The objective of this study was to investigate the efficacy of lipid emulsions encapsulated in calcium-alginate beads in reducing food intake and appetite sensations. These emulsion-alginate beads were ingested in a yogurt (active) and compared to an equienergetic yogurt containing nonencapsulated nutrients with comparable sensory properties (control) in a randomized placebo-controlled trial with crossover design. Thirty-three healthy overweight volunteers (mean age: 43 years; body mass index: 27.7 kg/m2; 14 male) received the 2 treatments. Test days started with a standardized small breakfast (t = 0) followed by an active or control yogurt (t = 90 minutes). Appetite sensations and gastrointestinal symptoms were monitored prior to and after consumption of the yogurt, and food intake was measured during ad libitum pasta meal consumption (t = 210 minutes). The hypothesis for this study was that delayed release of encapsulated lipids suppresses appetite sensations and reduces food intake. Food intake was significantly reduced with 51 ±â€¯20 kcal (213 ± 84 kJ) (P = .016) after intake of the active yogurt (770 ±â€¯38 kcal (3222 ± 159 kJ)) compared to the control (821 ±â€¯40 kcal (3435 ± 167 kJ)). The approach that we chose is promising to reduce food intake and could contribute to the development of an easy-to-use product for weight management.

Dietary fish oil, and to a lesser extent the fat-1 transgene, increases astrocyte activation in response to intracerebroventricular amyloid-ß 1-40 in mice.

OBJECTIVES: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer's disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear. METHODS: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-ß 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques. RESULTS: GFAP increased in all groups in response to amyloid-ß, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-ß infusion than wildtype safflower animals. CONCLUSION: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-ß 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-ß than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.

Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment.

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.

Oral administration of lipid oil-in-water emulsions performed with synthetic or protein-type emulsifiers differentially affects post-prandial triacylglycerolemia in rats

In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 mim diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (β-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry

Topically applied linoleic/linolenic acid for chronic migraine.

The topical application of linoleic and linolenic acids is a potential prophylactic approach to migraine via an anti-inflammatory mechanism. We present a 45-year-old woman with chronic migraine without aura. Previous use of abortive or prophylactic therapies including sumatriptan, amitriptyline and topiramate had failed due to lack of efficacy or side-effects, especially vomiting. In search of a topical agent she performed an n-of-1 trial comparing application of linoleic acid (safflower oil) versus oleic acid (olive oil) for migraine relief. She found safflower oil to be effective. Topically applied safflower oil rich in linoleic and linolenic acids may offer a safe, easily applied, well-tolerated, effective anti-inflammatory approach for the prophylactic treatment of chronic migraine.

Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection.

Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle. Animals were then euthanized at various time points for immunohistochemistry, gene expression, and lipidomic analyses. Peak microglial activation was observed at 5 days post-surgery and the resolution index was 10 days. Of the approximately 350 genes significantly changed over the 28 days post LPS injection, 130 were uniquely changed at 3 days post injection. No changes were observed in the bioactive mediator pools. However, a few lysophospholipid species were decreased at 24hr post surgery. When brain DHA is increased, microglial cell density did not resolve faster and did not alter gene expression. In conclusion, resolution of neuroinflammation appears to be independent of SPM. Increasing brain DHA had no effect in this model.

Effects of CD36 Genotype on Oral Perception of Oleic Acid Supplemented Safflower Oil Emulsions in Two Ethnic Groups: A Preliminary Study.

Previous studies demonstrate humans can detect fatty acids via specialized sensors on the tongue, such as the CD36 receptor. Genetic variation at the common single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially impact the perception of fatty acids, but comparative data among different ethnic groups are lacking. In a small cohort of Caucasian and East Asian young adults, we investigated if: (1) participants could detect oleic acid (C18:1) added to safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of oleic acid to safflower oil emulsions enhanced perception of fattiness and creaminess; and (3) variation at rs1761667 influenced oleic acid detection and fat taste perception. In a 3-alternate forced choice test, 62% of participants detected 2.9 ± 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess perception for the cohort as a whole, though East Asians carrying the GG genotype perceived more overall fattiness and creaminess than their AA genotype counterparts (P < 0.001). No differences were observed for the Caucasians. These preliminary findings indicate that free oleic acid can be detected in an oil-in-water emulsion at concentrations found in commercial oils, but it does not increase fattiness or creaminess perception. Additionally, variation at rs1761667 may have ethnic-specific effects on fat taste perception.

Observer-blind randomized controlled study of a cosmetic blend of safflower, olive and other plant oils in the improvement of scar and striae appearance.

OBJECTIVE: The normal process of skin tissue repair following injury invariably results in visual scarring. It is known that topical treatment with hydrophobic cosmetics rich in silicone and mineral oil content can improve the appearance of scars and striae. Given lifestyle preferences of many cosmetic consumers towards so-called natural treatments, the objective of this controlled randomized study was to investigate the efficacy of a plant body oil rich in oleic and linoleic acids (Bio Skin Oil® ) for improving the appearance of scars and striae. METHODS: A panel of 80 volunteers with non-hypertrophic scars (40) or stretch marks (40) not older than 3 years applied a cosmetic face and body oil for 8 weeks. Compared to an untreated scar/stretch mark region, a blinded investigator as well as volunteer assessments with given observed parameters demonstrated the efficacy of the oil under test. RESULTS: On the Observer Scar Assessment Scale (OSAS), the mean score was reduced on the product-treated area by approximately 5% (P = 0.006). The untreated area remained unchanged. Observed effects by volunteers were more pronounced - Patient Scar Assessment Scale (PSAS) giving a reduction of approximately 20% on the treated area, and on the control untreated area a reduction of approximately 6%. The overall product effect of 14% was shown to be clearly significant (P = 0.001). All statements relating to product traits achieved higher frequencies of agreements than of non-agreements and were therefore assessed positively by the volunteers. Highest frequencies of agreements occurred in statements that the test product provides a long-lasting, soft and supple skin feeling (93%); caring effect (87%); and quick absorbance (84%). Agreement was also found for statements that the product improves the skin appearance (61%) and that scars/striae appear less pronounced (51%). Only 17% of volunteers felt the oil had no benefit to the appearance of their scars/striae. CONCLUSIONS: The oil blend under test is effective in improving the appearance of non-keloid scars and striae. Further work is required to understand the mechanisms of how plant oil fatty acids ameliorate scar and striae appearance.

Altered gene expression of epigenetic modifying enzymes in response to dietary supplementation with linseed oil.

Recently we showed that 5% linseed oil (LSO) and 5% safflower oil (SFO) supplementation of cow's diets reduced milk fat yield by 30·38 and 32·42% respectively, accompanied by differential expression of genes and regulation by microRNAs (miRNA). This research communication addresses the hypothesis that epigenetic regulation could be involved in the observed milk fat reduction. Thus, this study investigated the gene expression pattern of major epigenetic modifying enzymes in response to dietary supplementation with LSO or SFO. Twenty-six Canadian Holstein cows in mid lactation were randomly assigned to two groups (13/group) and fed a control diet for 28 d (day -28 to -1) (control period- CP) followed by a treatment period (TP) (control diet supplemented with 5% LSO (LSO treatment) or 5% SFO (SFO treatment) of 28 d (day +1 to +28). After treatment, cows in the two groups were returned to the control diet for another 28 d (day +29 to +56) (post treatment period-PTP). Milk samples were collected on day -1 (CP), +7, +28 (TP) and +56 (PTP) for RNA isolation and measurement of the expression of thirteen epigenetic modifying genes including two DNA methytrasferases (DNMT1, DNMT3A), four histone acetylases (HAT1, KAT2A, KAT5 and CREBBP), five histone deacetylases (HDAC1, HDAC2, HDAC3, SIRT1 and SIRT2) and two histone methytransferases (EHMT2 and PRMT1) by qPCR. Linseed oil supplementation significantly repressed the expression of EHMT2, HDAC2 and HDAC3 on day +7 (P < 0·05) and KAT2A and SIRT2 on day +28 (P < 0·05) as compared with the control period (day -1) while SFO had no effect. When LSO was withdrawn, the expression of some of the genes increased slightly but did not reach control (day -1) levels at the end of the PTP. Our study demonstrated a significant role of LSO in the epigenetic regulation of fatty acid synthesis as compared to SFO. The effect of LSO may be related to its higher degree of unsaturation and might represent a different regulatory mechanism which needs further investigation.

The Impact of Virgin Coconut Oil and High-Oleic Safflower Oil on Body Composition, Lipids, and Inflammatory Markers in Postmenopausal Women.

This randomized crossover study compared the impact of virgin coconut oil (VCO) to safflower oil (SO) on body composition and cardiovascular risk factors. Twelve postmenopausal women (58.8 ± 3.7 year) consumed 30 mL VCO or SO for 28 days, with a 28-day washout. Anthropometrics included body weight and hip and waist circumference. Fat percent for total body, android and gynoid, fat mass, and lean mass were measured using dual-energy X-ray absorptiometry. Women maintained their typical diet recording 28 days of food records during the study. Results were analyzed with SPSS v24 with significance at P ≤ .05. Comparisons are reported as paired t-test since no intervention sequence effect was observed. VCO significantly raised total cholesterol, TC (+18.2 ± 22.8 mg/dL), low-density lipoprotein (+13.5 ± 16.0 mg/dL), and high-density lipoprotein, HDL (+6.6 ± 7.5 mg/dL). SO did not significantly change lipid values. TC and HDL were significantly different between test oils. The TC/HDL ratio change showed a neutral effect of both VCO and SO. One person had adverse reactions to VCO and increased inflammation. VCO decreased IL-1ß for each person who had a detected sample. The impact of VCO and SO on other cytokines varied on an individual basis. This was the first study evaluating the impact of VCO on body composition in Caucasian postmenopausal women living in the United States. Results are suggestive that individuals wishing to use coconut oil in their diets can do so safely, but more studies need to be conducted with larger sample sizes, diverse populations, and more specific clinical markers such as particle size.

Effects of PUFAs in a Mouse Model of HSV-1 Chorioretinitis.

PURPOSE: To examine the effects of n-3 and n-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) in a murine model of herpetic chorioretinitis. METHODS: BALB/c mice were fed on three high fat diets, which contained: Menhaden oil (rich in n-3 PUFAs); Safflower oil (rich in n-6 PUFAs); or Corn oil (rich in saturated fatty acids) as control group, 14 days previously and until 12 days following anterior chamber (AC) HSV-1 inoculation. RESULTS: Mice fed on Menhaden oil present an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also significant increase of RNA HSV-1 expression compared with Safflower and Corn oil groups. Furthermore, mice fed on Menhaden oil showed a significant decrease secretion of TNF-α, IFN-γ, IL-2 and IL-10 in splenic cells and both retinas. CONCLUSION: Our results showed that mice fed on Menhaden oil (n-3 PUFAs) presented an early development of contralateral chorioretinitis by day 6 post-AC HSV-1 inoculation and also a significant increase in RNA HSV-1 expression compared with animals fed on Safflower and Corn oils. This increase of HSV-1 could be associated with the higher development of chorioretinitis.

Enteral High Fat-Polyunsaturated Fatty Acid Blend Alters the Pathogen Composition of the Intestinal Microbiome in Premature Infants with an Enterostomy.

OBJECTIVE: To determine the effect of enteral fish oil and safflower oil supplementation on the intestinal microbiome in infants with an enterostomy born premature. STUDY DESIGN: Infants with an enterostomy born premature were randomized to receive early enteral supplementation with a high-fat polyunsaturated fatty acid (HF-PUFA) blend of fish oil and safflower oil vs standard nutritional therapy. We used 16S rRNA gene sequencing for longitudinal profiling of the microbiome from the time of study entry until bowel reanastomosis. We used weighted gene coexpression network analysis to identify microbial community modules that differed between study groups over time. We performed imputed metagenomic analysis to determine metabolic pathways associated with the microbial genes. RESULTS: Sixteen infants were randomized to receive enteral HF-PUFA supplementation, and 16 infants received standard care. The intestinal microbiota of infants in the treatment group differed from those in the control group, with greater bacterial diversity and lower abundance of Streptococcus, Clostridium, and many pathogenic genera within the Enterobacteriaceae family. We identified 4 microbial community modules with significant differences between groups over time. Imputed metagenomic analysis of the microbial genes revealed metabolic pathways that differed between groups, including metabolism of amino acids, carbohydrates, fatty acids, and secondary bile acid synthesis. CONCLUSION: Enteral HF-PUFA supplementation was associated with decreased abundance of pathogenic bacteria, greater bacterial diversity, and shifts in the potential metabolic functions of intestinal microbiota. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01306838.

A safflower oil based high-fat/high-sucrose diet modulates the gut microbiota and liver phospholipid profiles associated with early glucose intolerance in the absence of tissue inflammation.

SCOPE: Omega-6 (n-6) PUFA-rich diets are generally considered obesogenic in rodents. Here, we examined how long-term intake of a high-fat/high-sucrose (HF/HS) diet based on safflower oil affected metabolism, inflammation, and gut microbiota composition. METHODS AND RESULTS: We fed male C57BL/6J mice a HF/HS diet based on safflower oil-rich in n-6 PUFAs-or a low-fat/low-sucrose diet for 40 wk. Compared to the low-fat/low-sucrose diet, intake of the safflower-based HF/HS diet only led to moderate weight gain, while glucose intolerance developed at week 5 prior to signs of inflammation, but concurrent with increased levels of linoleic acid and arachidonic acid in hepatic phospholipids. Intake of the HF/HS diet resulted in early changes in the gut microbiota, including an increased abundance of Blautia, while late changes coincided with altered inflammatory profiles and increased fasting plasma insulin. Analysis of immune cells in visceral fat and liver revealed no differences between diets before week 40, where the number of immune cells decreased in the liver of HF/HS-fed mice. CONCLUSION: We suggest that a diet-dependent increase in the n-6 to omega-3 (n-3) PUFA ratio in hepatic phospholipids together with gut microbiota changes contributed to early development of glucose intolerance without signs of inflammation.

Changes in relative and absolute concentrations of plasma phospholipid fatty acids observed in a randomized trial of Omega-3 fatty acids supplementation in Uganda.

Expressing circulating phospholipid fatty acids (PLFAs) in relative concentrations has some limitations: the total of all fatty acids are summed to 100%; therefore, the values of individual fatty acid are not independent. In this study we examined if both relative and absolute metrics could effectively measure changes in circulating PLFA concentrations in an intervention trial. 66 HIV and HHV8 infected patients in Uganda were randomized to take 3g/d of either long-chain omega-3 fatty acids (1856mg EPA and 1232mg DHA) or high-oleic safflower oil in a 12-week double-blind trial. Plasma samples were collected at baseline and end of trial. Relative weight percentage and absolute concentrations of 41 plasma PLFAs were measured using gas chromatography. Total cholesterol was also measured. Intervention-effect changes in concentrations were calculated as differences between end of 12-week trial and baseline. Pearson correlations of relative and absolute concentration changes in individual PLFAs were high (>0.6) for 37 of the 41 PLFAs analyzed. In the intervention arm, 17 PLFAs changed significantly in relative concentration and 16 in absolute concentration, 15 of which were identical. Absolute concentration of total PLFAs decreased 95.1mg/L (95% CI: 26.0, 164.2; P=0.0085), but total cholesterol did not change significantly in the intervention arm. No significant change was observed in any of the measurements in the placebo arm. Both relative weight percentage and absolute concentrations could effectively measure changes in plasma PLFA concentrations. EPA and DHA supplementation changes the concentrations of multiple plasma PLFAs besides EPA and DHA.Both relative weight percentage and absolute concentrations could effectively measure changes in plasma phospholipid fatty acid (PLFA) concentrations.