Abstract 572: The Effect of Inflammation and Soluble Epoxide Hydrolase Inhibition on Fatty Acid Epoxide Incorporation Into VLDL

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Rachel E Walker ◽  
Olga V Savinova ◽  
Theresa L Pedersen ◽  
John W Newman ◽  
Gregory C Shearer

Objective: We have previously observed fatty acid epoxides, a class of potent anti-inflammatory oxylipins, in circulating VLDL. The source of these epoxides is unknown. Cytochrome P450 (CYP450) produces them via oxygenation of polyunsaturated fatty acids (PUFAs), and soluble epoxide hydrolase (sEH) converts them to diols. Our objectives were 1) to investigate if incorporation of epoxides into VLDL occurs via hepatic VLDL synthesis and 2) to determine if incorporation is modulated by inflammation or by inhibition of hepatic sEH. Approach and Results: A 2х2 factorial design was used for treatment assignment. Livers were isolated from rats treated with pro-inflammatory lipopolysaccharide (LPS, 10 mg/kg ip) or saline. AUDA, an inhibitor of sEH (10 μM), was included or excluded in the perfusate (Control, N=3; LPS, N=4; AUDA, N=4; LPS+AUDA, N=4). Livers were perfused for 180 minutes. VLDL was isolated by ultra-centrifugation, then analyzed by LC-MS/MS for oxylipin content. Analyzed epoxides and diols were derived from alpha-linolenic acid (ALA), linoleic acid (LA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Two-way ANOVA’s were used with triglyceride concentration as a covariate. Concentrations (nM) are reported as mean [95% CI]. DHA-derived epoxides increased with AUDA treatment (3.91 [3.01, 5.07]) compared to livers without AUDA (2.06 [1.58, 2.67]) (p=0.004), but other epoxides were unchanged by AUDA. EPA and ALA-derived epoxides decreased with LPS treatment (0.32 [0.22, 0.47]; 2.44 [2.07, 2.87]) compared to animals without LPS (0.73 [0.46, 1.16]; 3.28 [2.71, 3.96]) (p=0.01; 0.02). AA and DHA-derived diols decreased with LPS treatment (1.01 [0.82, 1.25]; 0.21 [0.17, 0.26]) compared to animals without LPS (1.46 [1.15, 1.86]; 0.31 [0.24, 0.39]) (p=0.03; 0.03). Conclusions: Treatment with LPS and AUDA have significant effects on incorporation of epoxides and diols into VLDL, supporting hepatic incorporation controlled by inflammation. Inflammation decreased select EPA- and ALA-derived epoxides. In contrast, sEH inhibition increased only DHA-derived epoxides. Surprisingly, in VLDL only epoxides derived from omega-3 fatty acids were affected by either inflammation or inhibition of sEH.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
William S. Harris ◽  
◽  
Nathan L. Tintle ◽  
Fumiaki Imamura ◽  
Frank Qian ◽  
...  

AbstractThe health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.


2017 ◽  
Vol 133 ◽  
pp. 79-87 ◽  
Author(s):  
Annika Irmgard Ostermann ◽  
Martina Reutzel ◽  
Nicole Hartung ◽  
Nicole Franke ◽  
Laura Kutzner ◽  
...  

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 138-138
Author(s):  
Mitchell M Norman ◽  
Nicolas Bland ◽  
Bradley M Boyd ◽  
Brianna Conroy ◽  
Chris Calkins ◽  
...  

Abstract A finishing study used 240 crossbred steers (initial BW=340 ±24 kg) to evaluate performance, carcass characteristics, and fatty acid profiles of beef from finishing steers. Four inclusions (0, 10, 20, 30 % DM basis) of Green Grass displaced dry rolled corn in the finishing diet. Green Grass is a blend of herbs and plants imported from Korea that are high in omega-3 fatty acids with 13.9 % fat,32.0 % CP, and 27.0 % Acid detergent fiber. The remaining diet consisted of 15 % WDGS, 20 % corn silage, and 6 % liquid supplement (DM basis). There were no differences in final BW, gain or carcass traits (P³0.14). Cattle were harvested over three slaughter days and were fed for 190, 199, or 203 days. Dry matter intake linearly increased (P = 0.04)as Green Grass inclusion increased in the diet. A linear response (P£0.01) to feeding Green Grass was observed for G:F, with steers fed Green Grass having lower feed efficiency than control cattle. The G:F of cattle fed Green Grass was 5.4, 3.4, and 6.8 % lower in G:F as inclusion increased suggesting Green Grass has 68.6 % the energy of corn it replaced. Steers fed 30 % Green Grass had a lower marbling score. Linear increases in alpha linolenic acid, trans-unsaturated fatty acids, and omega-3 fatty acids (P£0.01) were observed in steak samples from steers fed increasing inclusion of Green Grass. Including up to 30 % inclusion of Green Grass on a DM basis in finishing diets decreased G:F; however, it appeared to have no other effects on performance or carcass characteristics. Feeding Green Grass linearly improved omega-3 fatty acid concentration in beef.


Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1811
Author(s):  
Ella Aitta ◽  
Alexis Marsol-Vall ◽  
Annelie Damerau ◽  
Baoru Yang

Baltic herring (Clupea harengus membras) is one of the most abundant commercially caught fish species from the Baltic Sea. Despite the high content of fat and omega-3 fatty acids, the consumption of Baltic herring has decreased dramatically over the last four decades, mostly due to the small sizes and difficulty in processing. At the same time there is an increasing global demand for fish and fish oil rich in omega-3 fatty acids. This study aimed to investigate enzyme-assisted oil extraction as an environmentally friendly process for valorizing the underutilized fish species and by-products to high quality fish oil for human consumption. Three different commercially available proteolytic enzymes (Alcalase®, Neutrase® and Protamex®) and two treatment times (35 and 70 min) were investigated in the extraction of fish oil from whole fish and by-products from filleting of Baltic herring. The oil quality and stability were studied with peroxide- and p-anisidine value analyses, fatty acid analysis with GC-FID, and volatile compounds with HS-SPME-GC-MS. Overall, longer extraction times led to better oil yields but also increased oxidation of the oil. For whole fish, the highest oil yields were from the 70-min extractions with Neutrase and Protamex. Protamex extraction with 35 min resulted in the best fatty acid composition with the highest content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) but also increased oxidation compared to treatment with other enzymes. For by-products, the highest oil yield was obtained from the 70-min extraction with Protamex without significant differences in EPA and DHA contents among the oils extracted with different enzymes. Oxidation was lowest in the oil produced with 35-min treatment using Neutrase and Protamex. This study showed the potential of using proteolytic enzymes in the extraction of crude oil from Baltic herring and its by-products. However, further research is needed to optimize enzymatic processing of Baltic herring and its by-products to improve yield and quality of crude oil.


2015 ◽  
Vol 22 (3) ◽  
pp. 153-162 ◽  
Author(s):  
Juçara X. Zaparoli ◽  
Eduardo K. Sugawara ◽  
Altay A.L. de Souza ◽  
Sérgio Tufik ◽  
José Carlos F. Galduróz

Background: High oxidative stress, which is caused by smoking, can alter omega-3 fatty acid concentrations. Since omega-3 fatty acids play a role in dopaminergic neurotransmission related to dependence, it is important to understand their effects on nicotine dependence. Methods: This research comprised 2 studies. The first one consisted of a cross-sectional evaluation, in which the levels of the most important omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were compared between smokers and non-smokers in a sample of 171 individuals; of them, 120 were smokers and 51 were non-smokers. The other study was a clinical, double-blind, randomized, placebo controlled, in which 63 smokers received daily treatment with capsules of fish oil (a source of omega-3/3 g/day) or mineral oil (used as placebo, also 3 g/day), taken 3 times a day for 90 days. Each fish oil capsules contained approximately 210.99 mg EPA and 129.84 mg of DHA. The outcome was evaluated by means of psychometric and biological measures as well as self-reports of tobacco use. The evaluations were carried out at the beginning of treatment and once a month thereafter (total of 4 times). Outcomes: The omega-3 fatty acid lipid profile showed that smokers present lower concentrations of DHA. After treatment, the omega-3 group showed a significant reduction in their levels of dependence. Interpretation: Smokers showed lower peripheral levels of omega-3, and treatment with the most important omega-3 fatty acids brought about a reduction in nicotine dependence.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
C. Castro-Correia ◽  
S. Sousa ◽  
S. Norberto ◽  
C. Matos ◽  
V. F. Domingues ◽  
...  

Context. Several studies have shown a link between proinflammatory activity and the presence or deficit of some fatty acids. Inflammation is associated with several diseases including diabetes.Objective. To characterize and compare the fatty acids profiles in children with inaugural type 1 diabetes, diabetic children (at least 1 year after diagnosis), and healthy children.Design. Plasma fatty acids profiles in children with inaugural diabetes, children with noninaugural diabetes, and controls, all of whom were prepubescent with a BMI < 85th percentile, were evaluated.Results. Omega-3 fatty acid levels were higher in recently diagnosed subjects with diabetes than in controls. The ratio of omega-6/omega-3 fatty acids was higher in the control population. Omega-6 fatty acid levels were higher in the nonrecent diabetic subjects than in the children with recently diagnosed diabetes, and the levels were higher in the nonrecent diabetes group compared to the control group.Conclusion. Our findings showed higher levels of alpha-linolenic acid, EPA, and DHA, as well as mono- and polyunsaturated fatty acids, in diabetic children. These findings reinforce the importance of precocious nutritional attention and intervention in the treatment of diabetic children.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Claire Newlon ◽  
Matthew Muldoon ◽  
Susan Sereika ◽  
Dora Kuan

Background: Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome. Hypothesis: Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults Methods: We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled <300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat. Results: Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol. Conclusions: Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.


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