title: Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats.
abstract: Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.
authors: Dipartimento di Scienze e Tecnologie Biomediche, Università di Cagliari, Cagliari 09100, Italy.
authors: Barbara
authors: B
authors: Batetta
authors: Mikko
authors: M
authors: Griinari
authors: Gianfranca
authors: G
authors: Carta
authors: Elisabetta
authors: E
authors: Murru
authors: Alessia
authors: A
authors: Ligresti
authors: Lina
authors: L
authors: Cordeddu
authors: Elena
authors: E
authors: Giordano
authors: Francesca
authors: F
authors: Sanna
authors: Tiziana
authors: T
authors: Bisogno
authors: Sabrina
authors: S
authors: Uda
authors: Maria
authors: M
authors: Collu
authors: Inge
authors: I
authors: Bruheim
authors: Vincenzo
authors: V
authors: Di Marzo
authors: Sebastiano
authors: S
authors: Banni
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002828:Choristoma / Q000188:drug therapy / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D063388:Endocannabinoids; D033201:Euphausiacea; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005989:Glycerides / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D012758:Shellfish; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D004041:Dietary Fats; D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; C094503:glyceryl 2-arachidonate; C078814:anandamide