Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

Artmann, Andreas; Petersen, Gitte; Hellgren, Lars; Boberg, Julie; Skonberg, Christian; Nellemann, Christine; Hansen, Steen Honoré; Hansen, Harald S.

doi:10.1016/j.bbalip.2008.01.006

Cited by 300 publications

(286 citation statements)

References 76 publications

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“…All these findings are in line with the notion that enterocytes produce OEA in response to a fatty meal (mainly upon ingestion of oleic acid) (Artmann et al. 2008). Once intracellular OEA reaches the concentration of 300‐400 μ mol/L, it activates the PPAR α receptor (Schwartz et al.…”

Section: Discussionmentioning

confidence: 99%

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

et al. 2018

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The endogenous peroxisome proliferator‐activated receptor alpha (PPAR‐α) agonist Oleoylethanolamide (OEA) inhibits eating in rodents, mainly by delaying the onset of meals. The underlying mechanisms of OEA‐induced anorexia, however, remain unclear. Animals treated with high OEA doses were shown to display signs of discomfort and impaired locomotion. Therefore, we first examined whether the impaired locomotion may contribute to OEA's anorectic effect. Second, it is controversial whether abdominal vagal afferents are necessary for OEA's anorectic effect. Thus, we explored alternative peripheral neural pathways mediating IP OEA's anorectic effect by performing a celiac‐superior mesenteric ganglionectomy (CGX) or a subdiaphragmatic vagal deafferentation (SDA) alone or in combination. Exogenously administered OEA at a commonly used dose (10 mg/kg BW, IP) concurrently reduced food intake and compromised locomotor activity. Attempts to dissociate both phenomena using the dopamine D2/D3 receptor agonist Quinpirole (1 mg/kg BW, SC) failed because Quinpirole antagonized both, OEA‐induced locomotor impairment and delay in eating onset. CGX attenuated the prolongation of the latency to eat by IP OEA, but neither SDA nor CGX prevented IP OEA‐induced locomotor impairment. Our results indicate that IP OEA's anorectic effect may be secondary to impaired locomotion rather than due to physiological satiety. They further confirm that vagal afferents do not mediate exogenous OEA's anorectic effects, but suggest a role for spinal afferents in addition to an alternative, nonneuronal signaling route.

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Section: Discussionmentioning

confidence: 99%

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

et al. 2018

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“…These differences may be due to a highly activated EC system in HF-DIO mice as compared with that in regular-diet-supplied mice. 4,29 As Compound-1 is peripherally more selective and potent enough to discriminate the central and peripheral effects, we further examined the contribution of peripheral CB1 receptors in the antiobesity activities of CB1 antagonist using chronic animal models. In HF-DIO mice treated by 10 mg kg À1 of Compound-1, its plasma concentration was 7.6 times higher than that of 10 mg kg À1 SR141716A-treated HF-DIO mice (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control

et al. 2009

Int J Obes

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Objective: To investigate whether drugs targeting peripheral cannabinoid-1 (CB1) receptor ameliorate adiposity comparable to central CB1-receptor antagonist or not. Measurements: Receptor binding assay and functional assay in vitro. Pharmacokinetic parameters in mice, brain uptake clearance of compounds in rats and antagonism on the CB1-agonist-induced hypothermia in mice. Diet consumption, body weight changes, hepatic gene expression of sterol-regulatory element-binding protein-1 (SREBP-1) and plasma/tissue concentrations of compounds in HF diet-induced obese (HF-DIO) mice after acute and chronic treatment. Results: Compound-1, an SR141716A derivative, is a peripheral CB1-receptor-selective antagonist that is 10 times less potent than SR141716A in in vitro evaluations. Although the plasma concentrations of Compound-1 are five times higher than those of SR141716A, its potency is still 10 times lower than that of SR141716A in reducing the consumption of normal or HF diet by mice. Through evaluations of brain uptake and the effect on CB1-agonist-induced hypothermia, it was verified that the bloodbrain barrier (BBB) penetration of Compound-1 is much lower than that of SR141716A. In HF-DIO mice, chronic treatment by Compound-1 showed dose-dependent antiobesity activities, while its brain distribution was very low as compared with that of SR141716A. Compound-1's effective doses for antiobesity activity were just over 30 mg kg À1 . However, Compound-1 completely suppressed the elevated hepatic SREBP-1 expression even at 10 mg kg À1 . Conclusion: These results suggest that (1) central CB1 receptors mediate anorectic response of CB1-receptor antagonists and (2) peripheral modulations, including SREBP-1 expression, are not major mechanisms in the antiobesity effects of CB1-receptor antagonists.

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“…Previous studies have reported omega-3 PUFA supplementation reduces levels of 2-AG (and AEA) across a range of tissues, including the brain (Artmann et al, 2008;Batetta et al, 2009;Matias et al, 2008;Watanabe et al, 2003;Wood et al, 2010); however, these studies are based on long term administration protocols and the effects appear driven by displacement of AA from phospholipids and subsequent competition for biosynthetic enzymes. This displacement was not seen in the present study as neither treatment altered AA levels likely due to the low doses of DHA and EPA applied, and therefore, this observation of an acute effect of DHA and EPA on 2-AG levels must be considered novel.…”

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confidence: 99%

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

et al. 2016

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Running title: EPA, but not DHA induces proliferation in NSCs Abbreviations: AA, Arachidonic acid, AEA, anandamide, DHA. Docosahexaenoic acid; EPA, eicosapentaenoic acid, 2-AG, 2-arachidonylglycerol 2 Title: Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1 deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1 deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

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Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine

Cited by 300 publications

References 76 publications

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

Oleoylethanolamide-induced anorexia in rats is associated with locomotor impairment

Peripherally acting CB1-receptor antagonist: the relative importance of central and peripheral CB1 receptors in adiposity control

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

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