Abstract 702: Walnut Treatment Reduces Specific Pro-inflammatory Lipid Mediators While Increasing Anti-inflammatory Ones: An RCT subanalysis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Gregory C Shearer ◽  
John W Newman ◽  
Roberta R Holt ◽  
Carl L Keen ◽  
Robert M Hackman
Keyword(s):  
Fatty Acids ◽  
Heart Disease ◽  
Fatty Acid ◽  
Inflammatory Responses ◽  
Plasma Lipid ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Plasma Fatty Acid ◽  
Anti Inflammatory ◽  
Active Dose

Background: Lipid mediators are transported in plasma, inducing pro- or anti-inflammatory responses in target tissues. Each daily nut serving is associated with 30% reduction in risk for cardiovascular or ischemic heart disease. Walnuts are an abundant source of bioactives and of precursors to lipid mediator synthesis: linoleic (LA) and alpha-linolenic (aLA) acids. How walnuts impact plasma lipid mediators either by providing more substrate or more specifically via other bioactives is unknown. Objective: Measure lipid mediators from the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome p450 (CYP), and auto-oxidative pathways in plasma from subjects consuming large and small amounts of walnuts. Design: 40 hypercholesterolemic, postmenopausal females were randomly assigned to a null dose (5g/d) or an active dose (40 g/d) of walnuts for 4 weeks. In a subset of 20 subjects, plasma lipid mediators synthesized from LA, aLA and other polyunsaturated fatty acids were measured by LC/MS/MS at baseline and final visits. Differences are reported as mean, 95% CIs. Results: Walnuts did not alter the compositional abundance of any plasma fatty acid except aLA, which was increased 1.46 fold [1.83, 1.16], p=0.003. Walnuts did modify plasma lipid mediator composition: specific pro-inflammatory COX metabolites, PGD2 and PGJ2/delta-12-PGJ2 were reduced by -72% [-43, -86] and -55% [-9, -77] respectively. LOX metabolites were almost uniformly depressed: the immediate mid-chain alcohols of LA (HODEs), dgLA (HETrEs), AA (HETEs), EPA (HEPEs) and DHA (HDoHEs) were reduced by 50-75% (p≤0.007), but aLA (HOTEs) were not. Metabolites of 5-LOX further downstream were also reduced: 5-KETE by 79% [-91, -50], and 6-trans-LTB4 by -89% [-76, -95]. Conversely, anti-inflammatory CYP-epoxides of LA (EpOME) and aLA (EpODE) were increased 82% [3, 223] and 143% [37, 331]. Epoxides of eicosanoids and docosanoids were unchanged (AA EpETrEs or EETs; EPA EpETEs; DHA EpDPEs). Conclusion: Walnut feeding reduces plasma pro-inflammatory COX and LOX metabolites while increasing some anti-inflammatory CYP metabolites. The effect occurs largely without changes in fatty acids, suggesting a molecular mechanism independent of simple changes in precursor abundance.

scholarly journals Therapeutic Applicability of Anti-Inflammatory and Proresolving Polyunsaturated Fatty Acid-Derived Lipid Mediators

2010 ◽  
Vol 10 ◽  
pp. 676-712 ◽  
Author(s):  
Gerard L. Bannenberg
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Host Defense ◽  
Inflammatory Disease ◽  
Lipid Mediators ◽  
Molecular Pathways ◽  
Tissue Protection ◽  
Anti Inflammatory ◽  
Long Chain

The enzymatic oxygenation of polyunsaturated fatty acids by lipoxygenases and cyclo-oxygenases is a resourceful mode of formation of specific autacoids that regulate the extent and pace of the inflammatory response. Arachidonate-derived eicosanoids, such as lipoxin A4, prostaglandin (PG)D2, PGF2α, PGE2, and PGD2-derived cyclopentenones exert specific roles in counter-regulating inflammation and turning on resolution. Recently recognized classes of autacoids derived from long-chain ω-3 polyunsaturated fatty acids, the E- and D-series resolvins, protectin D1, and maresin 1, act as specialized mediators to dampen inflammation actively, afford tissue protection, stimulate host defense, and activate resolution. It is held that counter-regulatory lipid mediators and the specific molecular pathways activated by such endogenous agonists may be suitable for pharmacological use in the treatment of inflammatory disease. The anti-inflammatory drug aspirin is a striking example of a drug that is able to act in such a manner, namely through triggering the formation of 15-epi-lipoxin A4and aspirin-triggered resolvins. Different aspects of the therapeutic applicability of lipid mediators have been addressed here, and indicate that the development of innovative pharmacotherapy based on anti-inflammatory and proresolution lipid mediators presents novel prospects for the treatment of inflammatory disease.

scholarly journals Plasma fatty acid profile in dairy cows associated with the inclusion of annatto in their diet

2020 ◽  
Vol 42 ◽  
pp. e47651
Author(s):  
Clarissa Sampaio de Oliveira Lima ◽  
Albericio Pereira de Andrade ◽  
André Luiz Rodrigues Magalhães ◽  
Omer Cavalcanti de Almeida ◽  
Sebastião Inocêncio Guido ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Dairy Cows ◽  
Fatty Acid Profile ◽  
Plasma Lipid ◽  
High Density Lipoproteins ◽  
Plasma Fatty Acid ◽  
Randomized Design ◽  
Completely Randomized Design ◽  
Plasma Fatty Acid Profile

The objective of this study was to evaluate the plasma lipid profile and plasma fatty acids of dairy cows receiving diets supplemented with annatto. A total of 32 Holstein cows (550 kg), distributed in a completely randomized design, were allocated to individual stalls and submitted to following treatments: C0 = no annatto; C4 = inclusion of annatto at 4 g kg-1 dry matter (DM) of diet (0.07 g bixin kg-1 diet); C5 = inclusion of annatto at 5 g kg-1 DM of diet (0.09 g bixin kg-1 diet); and C7 = inclusion of annatto at 7 g kg-1 DM of diet (0.12 g bixin kg-1 diet). Blood samples were collected via epigastric vein puncture, centrifuged, and frozen for subsequent analysis. The results indicate that the inclusion (p > 0.05) of annatto does not decrease the total cholesterol or low and high density lipoproteins. However, it impacts the profile of fatty acids, evidenced by the reduction (p < 0.05) in levels of hypercholesterolemic fatty acids viz, myristic acid and palmitic acid.  It also causes an increase in the levels of arachidonic acid, rumenic acid, linoleic acid, and total polyunsaturated fatty acids. Therefore, bixin included in the diets of dairy cows induces changes in the plasma fatty acid profile.

scholarly journals Lipid droplets are required for lipid mediator production and cancer cell proliferation

2021 ◽  
Author(s):  
Toni Petan ◽  
Thomas O. Eichmann ◽  
Robert Zimmermann ◽  
Anja Pucer Janež ◽  
Jana Gerstmeier ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Cancer Cell ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Cancer Cell Proliferation ◽  
Membrane Phospholipids

Lipid droplets are dynamic organelles with a central role in fatty acid metabolism. They protect cells from lipotoxicity by sequestering excess fatty acids but also provide fatty acids for metabolic reactions and signalling events. Here we show that lipid droplet turnover in cancer cells is required for production of ω-3 and ω-6 polyunsaturated fatty acid (PUFA)-derived inflammatory lipid mediators, including eicosanoids and specialised pro-resolving mediators. We show that incorporation of PUFAs into triglycerides mediated by diacylglycerol acyltransferase 1 (DGAT1), and their release by adipose triglyceride lipase (ATGL), are required for cyclooxygenase- and lipoxygenase-dependent lipid mediator production and cancer cell proliferation. The human group X secreted phospholipase A2 (hGX sPLA2) drives the delivery of membrane-derived PUFAs into lipid droplets, while ATGL promotes the incorporation of lipid droplet-derived PUFAs into phospholipids. The group IVA cytosolic PLA2 (cPLA2α) acts on membrane phospholipids and complements ATGL in the regulation of PUFA trafficking between phospholipids and triglycerides. This study identifies lipid droplets as essential cellular hubs that control PUFA availability for production of lipid mediators involved in inflammation and tumorigenesis.

scholarly journals Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Signaling ◽  
Plasma Fatty Acid ◽  
Hepatic Triglyceride ◽  
Triglyceride Synthesis ◽  
Hepatic Glucose ◽  
Acid Esterification ◽  
Fatty Acid Esterification

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

scholarly journals Metabonomics Reveals Drastic Changes in Anti-Inflammatory/Pro-Resolving Polyunsaturated Fatty Acids-Derived Lipid Mediators in Leprosy Disease

2013 ◽  
Vol 7 (8) ◽  
pp. e2381 ◽  
Author(s):  
Julio J. Amaral ◽  
Luis Caetano M. Antunes ◽  
Cristiana S. de Macedo ◽  
Katherine A. Mattos ◽  
Jun Han ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Lipid Mediators ◽  
Anti Inflammatory

scholarly journals Ruminant fat intake improves gut microbiota, serum inflammatory parameter and fatty acid profile in tissues of Wistar rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Larissa de Brito Medeiros ◽  
Susana Paula Almeida Alves ◽  
Rui José Branquinho de Bessa ◽  
Juliana Késsia Barbosa Soares ◽  
Camila Neves Meireles Costa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Gut Microbiota ◽  
Wistar Rats ◽  
High Fat Diets ◽  
Serum Biochemical ◽  
Anti Inflammatory ◽  
Diet Intake ◽  
Fat Diets ◽  
Gut Microbiota Composition

AbstractThis study tested the hypothesis that naturally and industrially produced trans-fatty acids can exert distinct effects on metabolic parameters and on gut microbiota of rats. Wistar rats were randomized into three groups according to the diet: CONT-control, with 5% soybean oil and normal amount of fat; HVF-20% of hydrogenated vegetable fat (industrial); and RUM-20% of ruminant fat (natural). After 53 days of treatment, serum biochemical markers, fatty acid composition of liver, heart and adipose tissue, histology and hepatic oxidative parameters, as well as gut microbiota composition were evaluated. HVF diet intake reduced triglycerides (≈ 39.39%) and VLDL levels (≈ 39.49%). Trans-fatty acids levels in all tissue were higher in HVF group. However, RUM diet intake elevated amounts of anti-inflammatory cytokine IL-10 (≈ 14.7%) compared to CONT, but not to HVF. Furthermore, RUM intake led to higher concentrations of stearic acid and conjugated linoleic acid in all tissue; this particular diet was associated with a hepatoprotective effect. The microbial gut communities were significantly different among the groups. Our results show that ruminant fat reversed the hepatic steatosis normally caused by high fat diets, which may be related to the remodelling of the gut microbiota and its anti-inflammatory potential.

scholarly journals Dietary Patterns, Plasma Fatty Acid Profiles and Risk of Coronary Heart Disease and Type 2 Diabetes (P18-092-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jowy Seah Yi Hoong ◽  
Choon Nam Ong ◽  
Woon-Puay Koh ◽  
Jian-Min Yuan ◽  
Rob van Dam
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Fatty Acid ◽  
Dietary Patterns ◽  
Disease Risk ◽  
Red Meat ◽  
Plasma Fatty Acid ◽  
Response Variables

Abstract Objectives Reduced rank regression (RRR) can incorporate a priori biological hypotheses into exploratory techniques used to generate dietary patterns. No previous studies have used nutrition biomarkers including plasma fatty acids as response variables in RRR. We aimed to derive dietary patterns that explain variation in plasma fatty acid concentrations using RRR and evaluate these in relation to risk of coronary heart disease (CHD) and type 2 diabetes (T2D). Methods We derived dietary patterns in a subsample of 711 participants with fatty acid concentrations in the Singapore Chinese Health Study using RRR with 31 food groups/items as predictors and 10 plasma fatty acid biomarkers as response variables. Scores for the dietary patterns derived in the subset were then calculated among the full cohort. We followed up 58,065 and 45,411 men and women for CHD mortality and incident T2D respectively. Results We identified a ‘prudent pattern’ high in green vegetables, fruits and fish and low in rice, eggs and red meat, and a ‘low-meat pattern’ high in bread, margarine and fruits, and low in red meat, seafood and poultry. During 1077,170 and 494,741 person-years of follow-up, 3016 CHD mortality events and 5207 cases of T2D respectively were identified. Both the ‘prudent pattern’ [all adjusted HRs for extreme quintiles, 0.68 (95% CI: 0.60, 0.77); P-trend < 0.001] and ‘low-meat pattern’ [HR, 0.86 (95% CI: 0.76, 0.96); P-trend = 0.010] were associated with lower risk of CHD mortality. The ‘prudent pattern’ was not associated with T2D whereas the ‘low-meat pattern’ was inversely associated with T2D but appeared restricted to women [HR, 0.69 (95% CI: 0.61, 0.78); P-trend < 0.001; P-interaction for sex = 0.001]. Conclusions Using nutrition biomarkers as response variables in RRR may be a promising approach to generating dietary patterns predictive of noncommunicable chronic disease risk. Funding Sources This study was supported by the National Institutes of Health, USA. JYHS is supported by the NGS Scholarship. W-PK is supported by the National Medical Research Council, Singapore. Supporting Tables, Images and/or Graphs

scholarly journals Dietary DHA/EPA Ratio Changes Fatty Acid Composition and Attenuates Diet-Induced Accumulation of Lipid in the Liver of ApoE−/− Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Liang Liu ◽  
Qinling Hu ◽  
Huihui Wu ◽  
Xiujing Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Inflammatory Responses ◽  
Elevated Serum ◽  
Serum Levels ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Fa Composition

Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE−/− mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks. After treatment, the serum and hepatic FA compositions, serum biochemical parameters, liver injury, and hepatic lipid metabolism-related gene expression were determined. Our results demonstrated that dietary DHA/EPA changed serum and hepatic FA composition by increasing contents of n-6 and n-3 PUFAs and decreasing amounts of monounsaturated fatty acids (MUFAs) and the n-6/n-3 ratio. Among the three DHA/EPA groups, the DHA/EPA 2 : 1 group tended to raise n-3 PUFAs concentration and lower the n-6/n-3 ratio in the liver, whereas DHA/EPA 1 : 2 tended to raise n-6 PUFAs concentration and improve the n-6/n-3 ratio. DHA/EPA supplementation reduced the hepatic impairment of lipid homeostasis, oxidative stress, and the inflammatory responses in HFD-fed mice. The DHA/EPA 2 : 1 group had lower serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol and higher levels of adiponectin than HFD group. The DHA/EPA 1 : 2 group had elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, without significant change the expression of genes for inflammation or hepatic lipid metabolism among the three DHA/EPA groups. The results suggest that DHA/EPA-enriched diet with an n-6/n-3 ratio of 4 : 1 may reverse HFD-induced nonalcoholic fatty liver disease to some extent by increasing n-6 and n-3 PUFAs and decreasing the amount of MUFAs and the n-6/n-3 ratio.

scholarly journals n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions

2013 ◽  
Vol 72 (3) ◽  
pp. 326-336 ◽  
Author(s):  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Mechanisms Of Action ◽  
Lipid Mediators ◽  
Functional Responses ◽  
New Family ◽  
Epa And Dha ◽  
Novel Interactions

Numerous effects of n-3 fatty acids EPA and DHA on functional responses of cells involved in inflammation and immunity have been described. Fatty acid-induced modifications in membrane order and in the availability of substrates for eicosanoid synthesis are long-standing mechanisms that are considered important in explaining the effects observed. More recently, effects on signal transduction pathways and on gene expression profiles have been identified. Over the last 10 years or so, significant advances in understanding the mechanisms of action of n-3 fatty acids have been made. These include the identification of new actions of lipid mediators that were already described and of novel interactions among those mediators and the description of an entirely new family of lipid mediators, resolvins and protectins that have anti-inflammatory actions and are critical to the resolution of inflammation. It is also recognised that EPA and DHA can inhibit activation of the prototypical inflammatory transcription factor NF-κB. Recent studies suggest three alternative mechanisms by which n-3 fatty acids might have this effect. Within T-cells, as well as other cells of relevance to immune and inflammatory responses, EPA and DHA act to disrupt very early events involving formation of the structures termed lipid rafts which bring together various proteins to form an effective signalling platform. In summary, recent research has identified a number of new mechanisms of action that help to explain previously identified effects of n-3 fatty acids on inflammation and immunity.

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