scholarly journals Effects of EPA and DHA Supplementation on Plasma Specialized Pro-resolving Lipid Mediators and Blood Monocyte Inflammatory Response in Subjects with Chronic Inflammation (OR29-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jisun So ◽  
Nirupa Matthan ◽  
Krishna Maddipati ◽  
Alice Lichtenstein ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Plasma Concentrations ◽  
Plasma Phospholipid ◽  
Docosapentaenoic Acid ◽  
Blood Monocytes ◽  
High Oleic Sunflower Oil ◽  
Epa And Dha

Abstract Objectives The role of n-3 fatty acid-derived specialized pro-resolving mediators (SPMs), including the novel docosapentaenoic acid (DPA) products, in reducing inflammation in humans has not been determined. We evaluated the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on plasma SPMs and the resulting impact on the inflammatory response of peripheral blood monocytes. Methods In a randomized, controlled, crossover trial, 21 subjects (9 men and 12 women, 50–75 y) with chronic inflammation (C-reactive protein > 2 µg/mL) entered a 4-week lead-in control phase (high oleic sunflower oil, 3 g/d) and then two sequential 10-week supplementation phases with pure EPA or DHA (3 g/d each), separated by a 10-week washout phase. Plasma phospholipid (PL) fatty acid composition and SPMs, including their precursors, were measured at the end of each phase. Following lipopolysaccharides (LPS) stimulation, the inflammatory response of blood monocytes was assessed by inflammatory gene expression. Results EPA increased PL EPA (P < 0.001) and plasma concentrations of 18-HEPE, the precursor of the E-series resolvins (RvEs) (P < 0.001). The increase in plasma 18-HEPE concentrations, was associated with the increase in PL EPA (β = 14.9 pg/ml, P < 0.01). However, RvEs were undetectable. EPA increased PL DPA (P < 0.001) but not DPA-derived SPMs. DHA increased PL DHA and plasma concentrations of 17-HDHA and 14-HDHA, the precursors of DHA-derived SPMs (P < 0.001). DHA also significantly increased PL EPA and 18-HEPE (P < 0.001), suggesting some DHA retroconversion to EPA. Interestingly, DHA lowered PL DPA (P < 0.001) but increased the DPA-derived SPMs RvD5n-3 DPA and MaR1n-3 DPA (P < 0.001). In monocytes, while both EPA and DHA lowered the LPS-induced expression of TNFA(P < 0.03 and P < 0.001, respectively), TNFA expression was inversely correlated with plasma concentrations of MaR1n-3 DPA (ρ = −0.32, P < 0.04). Conclusions Relative to EPA, DHA supplementation increases a broader range of SPMs, with EPA and DHA differentially affecting PL DPA and DPA-derived SPMs. Plasma concentrations of MaR1n-3 DPA following EPA and DHA supplementation are associated with an attenuated inflammatory response in blood monocytes, suggesting a potential role of this SPM in reducing inflammation in humans. Funding Sources Funded by USDA/NIFA and Cohn Student Award. Supporting Tables, Images and/or Graphs

The Role of Dietary Lipid in the Regulation of Unconjugated Hyperbilirubinaemia in Gunn Rats

1979 ◽  
Vol 57 (4) ◽  
pp. 327-337 ◽  
Author(s):  
J. L. Gollan ◽  
D. R. Hole ◽  
Barbara H. Billing
Keyword(s):  
Fatty Acid ◽  
Plasma Concentrations ◽  
Dietary Lipid ◽  
Normal Diet ◽  
Degree Of Saturation ◽  
Bilirubin Concentration ◽  
Fatty Acid Chain ◽  
Gunn Rats ◽  
Plasma Bilirubin

1. The purpose of this study was to characterize the mechanisms of diet-induced hyperbilirubinaemia in Gunn rats with emphasis on the role of lipids, and to examine their relationship with regard to fasting hyperbilirubinaemia. 2. A lipid-free normocaloric diet produced a threefold increase in plasma bilirubin concentration (baseline 109.4 μmol/l), which was maximal by 10 days and thereafter remained constant. The level of hyperbilirubinaemia attained was not influenced by fasting or phenobarbitone, and returned to baseline concentration within 10 days of resuming a normal diet. 3. Determination of hepatic bilirubin showed that the magnitude of the hepatic bilirubin pool was increased by the lipid-free diet but was unchanged by fasting. Hepatic ligandin concentrations were comparable in fasted Gunn rats and those fed normal or lipid-free diets, although total hepatic ligandin was reduced in the fasted animals. 4. The hyperbilirubinaemic effect of the lipid-free diet was largely reversed by the inclusion of 10% lipid in the diet and was affected to a lesser extent by 5% lipid. Similar reductions in plasma bilirubin concentration were observed with a variety of other lipids (10%), regardless of their fatty acid chain length or degree of saturation. 5. In fasting animals a direct correlation was observed between plasma bilirubin and free fatty acid concentrations and insulin levels were greatly depressed, whereas in those fed on the lipid-free diet no significant changes were evident in plasma concentrations of free fatty acids or insulin. 6. Plasma bilirubin concentration was unrelated to alterations in plasma triglycerides produced by the administration of clofibrate. However, an unexplained decrease in plasma bilirubin (40%) without a significant change in triglycerides was noted when clofibrate was added to the lipid-free diet. 7. Analysis of kinetic data obtained from [14C]bilirubin clearance studies revealed that hyperbilirubinaemia associated with the lipid-free diet reflected a marked reduction (60%) in plasma clearance with no change in bilirubin turnover. This was accompanied by a relative redistribution of bilirubin from the extravascular pool to the plasma pool. 8. Although these studies indicate that fasting and the withdrawal of dietary lipid have some similar effects on bilirubin metabolism, it seems likely that different mechanisms are responsible for the hyperbilirubinaemia.

scholarly journals Regulation of macrophage migration by a novel plasminogen receptor Plg-RKT

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5622-5630 ◽  
Author(s):  
Shahrzad Lighvani ◽  
Nagyung Baik ◽  
Jenna E. Diggs ◽  
Sophia Khaldoyanidi ◽  
Robert J. Parmer ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Human Peripheral Blood ◽  
Plasminogen Activation ◽  
Blood Monocytes ◽  
Chemotactic Migration ◽  
Peripheral Blood Monocytes ◽  
Macrophage Recruitment ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

Abstract Localization of plasmin on macrophages and activation of pro–MMP-9 play key roles in macrophage recruitment in the inflammatory response. These functions are promoted by plasminogen receptors exposing C-terminal basic residues on the macrophage surface. Recently, we identified a novel transmembrane plasminogen receptor, Plg-RKT, which exposes a C-terminal lysine on the cell surface. In the present study, we investigated the role of Plg-RKT in macrophage invasion, chemotactic migration, and recruitment. Plg-RKT was prominently expressed in membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen activation by urokinase-type plasminogen activator (uPA) was markedly inhibited (by 39%) by treatment with anti–Plg-RKT mAb. Treatment of monocytes with anti–Plg-RKT mAb substantially inhibited invasion through the representative matrix, Matrigel, in response to MCP-1 (by 54% compared with isotype control). Furthermore, chemotactic migration was also inhibited by treatment with anti–Plg-RKT mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti–Plg-RKT mAb markedly inhibited macrophage recruitment (by 58%), concomitant with a reduction in pro–MMP-9 activation in the inflamed peritoneum. Treatment with anti–Plg-RKT mAb did not further reduce the low level of macrophage recruitment in plasminogen-null mice. We conclude that Plg-RKT plays a key role in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response.

scholarly journals Production of Monocyte Chemoattractant Protein 1 in Tuberculosis Patients

1998 ◽  
Vol 66 (5) ◽  
pp. 2319-2322 ◽  
Author(s):  
YuanGuang Lin ◽  
JianHua Gong ◽  
Ming Zhang ◽  
Wanfen Xue ◽  
Peter F. Barnes
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Lymph Nodes ◽  
Blood Monocytes ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tuberculosis Patients ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

ABSTRACT To investigate the role of monocyte chemoattractant protein 1 (MCP-1) in the immune response to Mycobacterium tuberculosis, we studied MCP-1 production in tuberculosis patients. CD14+ blood monocytes from tuberculosis patients spontaneously expressed higher levels of MCP-1 mRNA and protein than CD14+ monocytes from healthy tuberculin reactors. MCP-1 production in lymph nodes from tuberculosis patients was also markedly increased. These findings suggest that MCP-1 can contribute to the antimycobacterial inflammatory response by attracting monocytes and T lymphocytes.

scholarly journals Participation of the adrenal gland in the anti-inflammatory effect of polyunsaturated diets

1995 ◽  
Vol 4 (5) ◽  
pp. 359-363 ◽  
Author(s):  
V. L. F. Silveira ◽  
E. A. Limãos ◽  
D. W. Nunes
Keyword(s):  
Fatty Acid ◽  
Adrenal Gland ◽  
Inflammatory Response ◽  
Significant Inhibition ◽  
Carrageenin Oedema ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Carrageenin Injection ◽  
Inflammatory Effect

The effect of an n-3 (fish) and n-6 (soybean) fatty acid-rich diet on carrageenin paw oedema in rats, and the participation of adrenal gland, corticosterone and α2-macroglobulin (α2-M) in this process were studied. A significant inhibition of carrageenin oedema was observed not only in rats fed a diet rich in fish oil but also in the soybean group. α2-M was not detectable before carrageenin injection, suggesting that this putative antiinflammatory factor does not participate in the observed anti-inflammatory effect. Corticosterone levels were higher in fat-fed than in control rats, before carrageenin stimulus and adrenalectomy abolished the anti-inflammatory response in fat-fed animals, showing the important role of the adrenocortical hormones in this process.

scholarly journals Fish Oil Improves Pathway-Oriented Profiling of Lipid Mediators for Maintaining Metabolic Homeostasis in Adipose Tissue of Prediabetic Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriel Dasilva ◽  
Salomé Lois ◽  
Lucía Méndez ◽  
Bernat Miralles-Pérez ◽  
Marta Romeu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Response ◽  
White Adipose Tissue ◽  
Lipid Mediators ◽  
Tissue Homeostasis ◽  
Enzymatic Oxidation ◽  
Fish Oils ◽  
Compensatory Mechanism ◽  
Epa And Dha

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.

Advanced oxidation protein products and inflammatory markers in liver cirrhosis: a comparison between alcohol-related and HCV-related cirrhosis.

2011 ◽  
Vol 58 (1) ◽  
Author(s):  
Jolanta Zuwała-Jagiełło ◽  
Monika Pazgan-Simon ◽  
Krzysztof Simon ◽  
Maria Warwas
Keyword(s):  
Oxidative Stress ◽  
Liver Cirrhosis ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Inflammatory Markers ◽  
Antioxidant Defense ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Advanced Oxidation ◽  
Advanced Oxidation Protein Products

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.

Chronic kidney disease promotes chronic inflammation in visceral white adipose tissue

2017 ◽  
Vol 312 (4) ◽  
pp. F689-F701 ◽  
Author(s):  
Dong Mei Xiang ◽  
Xiu Zhen Song ◽  
Zhan Mei Zhou ◽  
Yang Liu ◽  
Xiao Yan Dai ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Chronic Inflammation ◽  
White Adipose Tissue ◽  
Metabolic Disturbance ◽  
Reduced Activity

White adipose tissue plays an important role in the development of metabolic disturbance, which is a common feature in patients with chronic kidney disease (CKD). The effect of CKD on white adipose tissue remains poorly appreciated. Here, we evaluated the inflammatory potential of visceral white adipose tissue in a rat model of CKD. The results showed that production of proinflammatory cytokines and infiltration of macrophage in the tissue were increased significantly in CKD rats compared with sham rats. Moreover, the primary adipocytes and stromal vascular fraction under the condition of CKD could trigger the inflammatory response in each other. Free fatty acid induced robust inflammatory response in ex vivo peritoneal-derived macrophages from CKD rats, which was associated with reduced activity of silent information regulator T1 (SIRT1). Improvement of SIRT1 activity by an activator could alleviate free fatty acid-induced inflammatory response in the macrophages and inflammation in the white adipose tissue. Moreover, oxidative stress occurred in the tissue and linked with the reduced activity of SIRT1 in macrophages and enhanced release of free fatty acid in the tissue. We thus identified CKD as a risk factor for chronic inflammation in white adipose tissue. These observations might open up new therapeutic strategies for metabolic disturbance in CKD via the modulation of adipose tissue-related pathways.

scholarly journals The Omega-3 Fatty Acids EPA and DHA, as a Part of a Murine High-Fat Diet, Reduced Lipid Accumulation in Brown and White Adipose Tissues

2019 ◽  
Vol 20 (23) ◽  
pp. 5895 ◽  
Author(s):  
Nikul Soni ◽  
Alastair B. Ross ◽  
Nathalie Scheers ◽  
Intawat Nookaew ◽  
Britt G. Gabrielsson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Inflammatory Response ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Corn Oil ◽  
High Fat ◽  
Adipose Tissues ◽  
Epa And Dha ◽  
Brown Adipose

Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatory response, but the mechanisms are unclear, especially at the tissue level. Adipose tissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal white and brown adipose tissues. HFD-ED fed mice showed reduced lipid accumulation and levels of the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared with HFD-corn oil fed animals. The transcriptomic analysis showed changes in β-oxidation pathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues.

scholarly journals Is There a Link between Zinc Intake and Status with Plasma Fatty Acid Profile and Desaturase Activities in Dyslipidemic Subjects?

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 93 ◽  
Author(s):  
Marija Knez ◽  
Ana Pantovic ◽  
Milica Zekovic ◽  
Zoran Pavlovic ◽  
Maria Glibetic ◽  
...  
Keyword(s):  
Trace Elements ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Fatty Acid Profile ◽  
Acid Composition ◽  
Plasma Concentrations ◽  
Absorption Spectrometry ◽  
Prevalence Of Obesity ◽  
Zn Status

The prevalence of obesity and dyslipidemia has increased worldwide. The role of trace elements in the pathogenesis of these conditions is not well understood. This study examines the relationship between dietary zinc (Zn) intake and plasma concentrations of Zn, copper (Cu) and iron (Fe) with lipid profile indicators, fatty acid composition in plasma phospholipids and desaturase enzyme activities in a dyslipidemic population. The role of the newly proposed biomarker of Zn status, the linoleic:dihomo-gama-linolenic acid (LA:DGLA) ratio, in predicting Zn status of dyslipidemic subjects has been explored. The study included 27 dyslipidemic adults, 39–72 years old. Trace elements were determined using atomic absorption spectrometry and fatty acid composition by a liquid gas chromatography. Desaturase activities were calculated from product-precursor fatty acid ratios. Dietary data were obtained using 24 h recall questionnaires. Insufficient dietary intake of Zn, low plasma Zn concentrations and an altered Cu:Zn ratio is related to modified fatty acid profile in subjects with dyslipidemia. Plasma Zn status was associated with obesity. There was no correlation between dietary Zn intake and plasma Zn status. The LA:DGLA ratio was inversely linked to dietary Zn intake. Cu, in addition to Zn, may directly or indirectly, affect the activity of desaturase enzymes.

Sign in / Sign up

Export Citation Format

Share Document