n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice

Watanabe, Shiro; Doshi, Masaru; Hamazaki, Tomohito

doi:10.1016/s0952-3278(03)00056-5

Cited by 136 publications

(87 citation statements)

References 33 publications

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“…17,[40][41][42] Also the fatty acid composition of dietary fat may influence endocannabinoid action. 43 For example, the presence or absence of n-3 PUFAs in the diet affects endocannabinoid levels in the brain, as shown by Berger et al 44 and Watanabe et al 45 Batetta et al 46 recently found that dietary n-3 PUFAs can reduce inflammatory markers and liver triglyceride levels, and these effects were associated with lower levels of endocannabinoid ligands in peripheral organs. Finally, there is an in vitro study showing that n-3 PUFA can reduce the levels of both anandamide and 2-AG in differentiated mouse adipocytes, whereas n-6 PUFAs (that is, arachidonic acid) were found to increase endocannabinoid levels.…”

Section: Discussionmentioning

confidence: 95%

Metabolic responses to long-term pharmacological inhibition of CB1-receptor activity in mice in relation to dietary fat composition

et al. 2009

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Background and objectives:The antiobesity effects of suppressed endocannabinoid signaling may rely, at least in part, on changes in lipid fluxes. As fatty acids exert specific effects depending on their level of saturation, we hypothesized that the dietary fatty acid composition would influence the outcome of treatment with a CB 1 -receptor antagonist (rimonabant). Methods: Mice were treated with rimonabant (10 mg kg À1 body weight per day) or vehicle while equicalorically fed either a low-fat diet (LF), a high-fat (HF) diet or an HF diet in which 10% of the saturated fatty acids (SFAs) were replaced by polyunsaturated fatty acids (PUFA) from fish oil (FO). Food intake and body weight were registered daily. Indirect calorimetry was performed and feces were collected. After 3 weeks, mice were killed for blood and tissue collection. Results: Relative to the LF diet, the HF diet caused anticipated metabolic derangements, which were partly reversed by the HF/FO diet. The HF/FO diet, however, was most obesity-promoting despite inhibiting lipogenesis as indicated by low gene expression levels of lipogenic enzymes. On all three diets, rimonabant treatment improved metabolic derangements and led to significantly lower body weight gain than their respective controls. This latter effect appeared largest in the HF/FO group, but occurred without major changes in nutrient absorption and energy expenditure. Conclusion: The effects of chronic rimonabant treatment on body weight gain occurred irrespective of diet-induced changes in lipogenic activity, food intake and daily energy expenditure, and were, in fact, most pronounced in HF/FO mice. The effects of dietary PUFA replacement in an HF diet on expansion of adipose tissue might allow the favorable effects of dietary PUFA on dyslipidemia and hepatic steatosis. In light of other disadvantageous effects of weight gain, this might be a risky trade-off.

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Section: Discussionmentioning

confidence: 95%

Metabolic responses to long-term pharmacological inhibition of CB1-receptor activity in mice in relation to dietary fat composition

et al. 2009

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“…AA and DHA are supplied to the brain from the circulation, either from dietary sources or as synthesized primarily in the liver from shorter-chain essential fatty acids ( 19,20 ). Dietary fatty acids thus exert particularly stringent substrate control over brain phospholipid production and are principal determinants of neuronal phospholipid composition (18)(19)(20)(21)(22)(23)(24). Adequate intake of DHA and/or eicosapentaenoic acid ([20:5( -3)]; EPA) is critical to normal brain development, structure, and function, and supports health (25)(26)(27).…”

Section: Lc-ms/ms Metabolomic Analysismentioning

confidence: 99%

“…The devastating infl ammatory effects of certain AAderived metabolites ( 30 ) and the health benefi ts of nutritive -3 fatty acid supplementation in the central nervous system and periphery ( 21,22,(25)(26)(27)(28)(29) have prompted in vivo fatty acid feeding studies that generally corroborate a positive association between DHA, EPA, or AA intake and the level of that respective fatty acid or their endocannabinoid-related ethanolamide and monoglyceride derivatives in various tissues and/or plasma ( 12,13,16,23,24,(31)(32)(33). The impact of DHA consumption on the various endocannabinoid-related metabolites in compartments where endocannabinoid signaling carries particular (patho)physiological and/or diagnostic import, such as brain and the blood circulation, has not been comprehensively examined in vivo ( 3,29,34,35 ).…”

Section: Lc-ms/ms Metabolomic Analysismentioning

confidence: 99%

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

Wood

Williams

Pandarinathan

et al. 2010

Journal of Lipid Research

123

110

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The endocannabinoid system includes two G-protein coupled cannabinoid receptors (CB1 and CB2), their endogenous lipid ligands (endocannabinoids), and the enzymes and transporters that help regulate cannabinergic tone ( 1 ). Endocannabinoid signaling is ubiquitous in mammals, being particularly critical in brain , where it modulates neurotransmitter release and exhibits neuroprotective effects ( 2, 3 ). Although the fi rst two endocannabinoids identifi ed, N -arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (AG), have been extensively characterized, the (patho)physiological impact of endocannabinoid signaling has prompted the search for additional endocannabinoids and their related metabolites/ biosynthetic precursors, creating an evolving network of chemical species collectively termed the endocannabinoid metabolome, few of which have been functionally annotated ( 1,(3)(4)(5)(6)(7)(8)(9). Although the translational and diagnostic aspects of endocannabinoid signaling are well appreciated ( 10, 11 ), factors that infl uence and regulate the endocannabinoid metabolome profi le among various tissues and compartments remains incompletely described and understood ( 1, 10 ), as are the metabolome's relationship to lipid pathways outside of the endocannabinoid signaling system ( 3, 9 ). Abstract

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“…In particular, foods relatively rich in o6 PUFAs, such as in many 'high-fat diets', can significantly enhance the levels of anandamide 31 and 2-AG. 32 On the other hand, as opposed to short-term food deprivation, long-term semistarvation reduces the hypothalamic levels of 2-AG in adult mice, 33 and of anandamide in pups from undernourished rat dams. 34 …”

Section: Endogenous Cannabinoids In the Brain And Peripheral Tissues mentioning

confidence: 99%

Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake

2006

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Endocannabinoids were first defined in 1995 as 'endogenous substances capable of binding to and functionally activating the cannabinoid receptors'. To date, two well-established endocannabinoids, N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), as well as a few other putative ligands, all derived from long-chain polyunsaturated fatty acids, have been identified in animal tissues. The biosynthetic and metabolic pathways for anandamide and 2-AG have been elucidated, and most of the enzymes therein involved have been cloned. We now know that CB 1 receptors, and endocannabinoids in tissue concentrations sufficient to activate them, are more widely distributed than originally thought, and are found in brain and peripheral organs involved in the control of energy intake and processing, including the hypothalamus, nucleus accumbens, brainstem, vagus nerve, gastrointestinal tract, adipose tissue and liver. Endocannabinoid biosynthetic and inactivating pathways are under the regulation of neuropeptides and hormones involved in energy homeostasis, and endocannabinoid levels are directly affected by the diet. Endocannabinoids, in turn, regulate the expression and action of mediators involved in nutrient intake and processing. These cross-talks are at the basis of the proposed role of endocannabinoid signalling in the control of food intake, from invertebrates to lower vertebrates and mammals, and their perturbation appears to contribute to the development of eating disorders. and CB 2 receptors share very little homology, thus pointing to a very early separation of the two encoding genes during animal evolution. Indeed, the only cannabinoid receptor ortholog fully sequenced in an invertebrate species, the sea squirt Ciona intestinalis (chordata), exhibits low homology with both mammalian subtypes. 4 Orthologs of CB 1 receptors have been found so far in lower vertebrates, including fish, amphibians and birds. 4 Clearly, cannabinoid receptors have not been selected by millions of years of evolution to be activated by D 9 -THC. It is now known that these receptors serve as targets for endogenous compounds of lipophilic nature, the endocannabinoids (Figure 1). The two best studied endocannabinoids are anandamide (arachidonoylethanolamide) 5 and 2-arachidonoylglycerol. 6,7 The activation by these compounds of CB 1 receptors expressed in presynaptic neurons results in inhibition of both excitatory and inhibitory neurotransmitter release in various brain areas, including those involved in food intake, 8,9 often with the subsequent establishment of both short-and long-term forms of neuronal plasticity. 10 In fact, endocannabinoids are biosynthesised 'de novo' and 'on demand' (i.e. only when and where needed) within the framework of phospholipid metabolic reactions, to be immediately released from the cell in order to activate their targets, and then rapidly removed from the extracellular space by rapid and selective uptake into the cell followed byCorrespondence: Dr V Di Marzo,

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n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice

Cited by 136 publications

References 33 publications

Metabolic responses to long-term pharmacological inhibition of CB1-receptor activity in mice in relation to dietary fat composition

Metabolic responses to long-term pharmacological inhibition of CB1-receptor activity in mice in relation to dietary fat composition

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake

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