Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet

Balvers, Michiel G.J.; Verhoeckx, Kitty; Meijerink, Jocelijn; Bijlsma, Sabina; Rubingh, Carina M.; Wortelboer, Heleen M.; Witkamp, Renger F.

doi:10.1016/j.intimp.2012.03.022

Cited by 50 publications

(27 citation statements)

References 44 publications

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“…Both compounds were already effective at concentrations as low as 1 nM. Interestingly and similar to what has been shown for anandamide during inflammation, DHEA and EPEA tissue levels were found to increase after an inflammatory stimulus in mice fed fish oil (Balvers et al, 2012b). This could indicate that these compounds have a role as endogenous anti-inflammatory mediators.…”

Section: Anti-inflammatory Propertiessupporting

confidence: 74%

N‐acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

Meijerink

Balvers

Witkamp

2013

British J Pharmacology

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N–3 long‐chain polyunsaturated fatty acids (n–3 LC‐PUFAs), in particular α‐linolenic acid (18:3n‐3), eicosapentaenoic acid (EPA; 20:5n‐3) and docosahexaenoic acid (DHA; 22:6n‐3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n–3 LC‐PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n–3 LC‐PUFA‐derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n–3 LC‐PUFA‐derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease. Linked Articles This article is part of a themed section on Cannabinoids. To view the other articles in this section visit &

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Section: Anti-inflammatory Propertiessupporting

confidence: 74%

N‐acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

Meijerink

Balvers

Witkamp

2013

British J Pharmacology

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“…The peak circulating concentration (C max ) of ibuprofen achieved in subjects in the NSAID group was 25.65 Ϯ 3.78 Serum arachidonic acid. During animal models of experimental inflammation, AA is the predominant substrate for elevated lipid mediator biosynthesis, as well as itself being elevated in systemic circulation as free circulating substrate (2,5,32). We found that circulating free AA increased significantly (P Ͻ 0.05) above baseline levels in human serum in both the placebo and ibuprofen groups at 90 min postexercise (ϳ1.3-fold) (Fig.…”

Section: Nsaid Kineticsmentioning

confidence: 63%

“…Prostanoids, including thromboxane (TXA 2 ) and the four primary biologically active prostaglandins-PGE 2 , PGD 2 , PGF 2␣ , and PGI 2 -are the major metabolic products of the COX-1 and COX-2 pathways, which induce/regulate inflammatory responses (75), and blockade of their synthesis is a well-characterized mechanism of action of NSAIDs (74). TXA 2 is a transient platelet COX-1 product, which is a potent arterial vasoconstrictor and platelet aggregator involved in blood coagulation before undergoing rapid nonenzymatic degradation to the inactive metabolites TXB 2 (Fig. 4).…”

Section: Nsaid Kineticsmentioning

confidence: 99%

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Markworth

Vella

Lingard

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

139

158

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Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0 -3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2␣, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery. eicosanoid; exercise; inflammation; nonsteroidal anti-inflammatory drug; resolution LIPID MEDIATORS ARE A DIVERSE class of bioactive autocrine/ paracrine signaling molecules that are synthesized endogenously from essential omega-6 and omega-3 fatty acids. Oxidation of free fatty acid substrates via cyclooxygenase (COX-1 and COX-2), lipoxygenase (5-LOX, 12-LOX, and 15-LOX), epoxygenase (CYP), and nonenzymatic pathways, produces a potential array of more than 100 distinct lipid mediators. Bioactive lipid mediators are involved in a wide range of physiological and pathological processes, one of the best characterized of which is their key role in the inflammatory response (reviewed in Ref. 91). Classical eicosanoids derived from omega-6 arachidonic acid (AA, -6 20:4), including prostaglandins (PGs; synthesized via COX-1 and COX-2) and leukotrienes (LTs, synthesized via 5-LOX), are well established proinflammatory signaling molecules that stimul...

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“…Similarly, mice with LPS-induced sepsis demonstrated different oxylipid profiles among various tissue locations (Balvers et al, 2012). Consequently, oxylipid concentrations in one biological sample cannot be used to infer oxylipid profiles in a different anatomic area.…”

Section: Discussionmentioning

confidence: 99%

Polyunsaturated fatty acids influence differential biosynthesis of oxylipids and other lipid mediators during bovine coliform mastitis

Mavangira¹,

Gandy²,

Zhang

et al. 2015

Journal of Dairy Science

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Coliform mastitis is a severe and sometimes fatal disease characterized by an unregulated inflammatory response. The initiation, progression, and resolution of inflammatory responses are regulated, in part, by potent oxylipid metabolites derived from polyunsaturated fatty acids. The purpose of this study was to characterize the biosynthesis and diversity of oxylipid metabolites during acute bovine coliform mastitis. Eleven cows diagnosed with naturally occurring acute systemic coliform mastitis and 13 healthy control cows, matched for lactation number and days in milk, were selected for comparison of oxylipid and free fatty acid concentrations in both milk and plasma. Oxylipids and free fatty acids were quantified using liquid chromatography-tandem mass spectrometry. All polyunsaturated fatty acids quantified in milk were elevated during coliform mastitis with linoleic acid being the most abundant. Oxylipids synthesized through the lipoxygenase and cytochrome P450 pathways accounted for the majority of the oxylipid biosynthesis. This study demonstrated a complex and diverse oxylipid network, most pronounced at the level of the mammary gland. Substrate availability, biosynthetic pathways, and degree of metabolism influence the biosynthesis of oxylipids during bovine coliform mastitis. Further studies are required to identify targets for novel interventions that modulate oxylipid biosynthesis during coliform mastitis to optimize inflammation.

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Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet

Cited by 50 publications

References 44 publications

N‐acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

N‐acyl amines of docosahexaenoic acid and other n–3 polyunsatured fatty acids – from fishy endocannabinoids to potential leads

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

Polyunsaturated fatty acids influence differential biosynthesis of oxylipids and other lipid mediators during bovine coliform mastitis

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