title: 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.
abstract: Eicosanoids and endocannabinoids/N-acylethanolamines (NAEs) are fatty acid derived compounds with a regulatory role in inflammation. Considering their complex metabolism, it is likely that inflammation affects multiple compounds at the same time, but how lipid profiles change in plasma and other tissues after an inflammatory stimulus has not been described in detail. In addition, dietary fish oil increases levels of several n-3 fatty acid derived eicosanoids and endocannabinoids, and this may lead to a broader change in the profiles of bioactive lipids. In the present study mice were fed a diet containing 3% w/w fish oil for 6 weeks before receiving i.p. saline or 3 mg/kg lipopolysaccharide (LPS) to induce an inflammatory response. Eicosanoid and endocannabinoid/NAE levels (in total 61 metabolites) in plasma, liver, ileum, and adipose tissue were quantified using targeted lipidomics after 2, 4, 8, and 24 h, respectively. Tissue- and time-dependent effects of LPS on bioactive lipid profiles were observed. For example, levels of CYP derived eicosanoids in the ileum were markedly affected by LPS, whereas this was less pronounced in the plasma and adipose tissue. For some compounds, such as 9,10-DiHOME, opposing effects of LPS were seen in the plasma compared to the other tissues, suggesting differential regulation of bioactive lipid levels after an inflammatory stimulus. Taken together, our results show that plasma levels do not always correlate with the effects found in the tissues, which underlines the need to measure profiles and pathways of mediators involved in inflammation, including endocannabinoid-like structures, in both plasma and tissues.
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands.
authors.forename: Michiel G J
authors.initials: MG
authors.lastname: Balvers
authors.forename: Kitty C M
authors.initials: KC
authors.lastname: Verhoeckx
authors.forename: Jocelijn
authors.initials: J
authors.lastname: Meijerink
authors.forename: Sabina
authors.initials: S
authors.lastname: Bijlsma
authors.forename: Carina M
authors.initials: CM
authors.lastname: Rubingh
authors.forename: Heleen M
authors.initials: HM
authors.lastname: Wortelboer
authors.forename: Renger F
authors.initials: RF
authors.lastname: Witkamp
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000097:blood / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015777:Eicosanoids / Q000097:blood / Q000378:metabolism*; D063388:Endocannabinoids; D005395:Fish Oils / Q000008:administration & dosage*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D063385:Cannabinoid Receptor Modulators; D004042:Dietary Fats, Unsaturated; D015777:Eicosanoids; D063388:Endocannabinoids; D005395:Fish Oils; D008070:Lipopolysaccharides