Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats

Marzo, Vincenzo Di; Griinari, Mikko; Carta, Gianfranca; Murru, Elisabetta; Ligresti, Alessia; Cordeddu, Lina; Giordano, Elena; Bisogno, Tiziana; Collu, Maria; Batetta, Barbara; Uda, Susumu; Berge, Kjetil; Banni, Sebastiano

doi:10.1016/j.idairyj.2009.11.015

Cited by 76 publications

(67 citation statements)

References 26 publications

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“…Decreases in both AEA and 2-AG, with the former persisting after HFD challenge, were observed in the LIN group compared with the SAF group. On the whole, these findings, in agreement with previous data in adult mice (35) and rats (34,36), confirm that early dietary interventions based on n-3 FA, might constitute an alternative strategy to "global" CB1R blockers to reduce ECS overactivity and, subsequently, various parameters of the metabolic syndrome, while possibly limiting the consequences on brain function.…”

Section: Discussionsupporting

confidence: 90%

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Demizieux

Piscitelli²,

Troy-Fioramonti

et al. 2016

Diabetes

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Evidence suggests that alterations of glucose and lipid homeostasis induced by obesity are associated with the elevation of endocannabinoid tone. The biosynthesis of the two main endocannabinoids, N-arachidonoylethanolamine and 2-arachidonoyl-glycerol, which derive from arachidonic acid, is influenced by dietary fatty acids (FAs). We investigated whether exposure to n-3 FA at a young age may decrease tissue endocannabinoid levels and prevent metabolic disorders induced by a later high-fat diet (HFD) challenge. Three-week-old mice received a 5% lipid diet containing lard, lard plus safflower oil, or lard plus linseed oil for 10 weeks. Then, mice were challenged with a 30% lard diet for 10 additional weeks. A low n-6/n-3 FA ratio in the early diet induces a marked decrease in liver endocannabinoid levels. A similar reduction was observed in transgenic Fat-1 mice, which exhibit high tissue levels of n-3 FA compared with wild-type mice. Hepatic expression of key enzymes involved in carbohydrate and lipid metabolism was concomitantly changed. Interestingly, some gene modifications persisted after HFD challenge and were associated with improved glycemic control. These findings indicate that early dietary interventions based on n-3 FA may represent an alternative strategy to drugs for reducing endocannabinoid tone and improving metabolic parameters in the metabolic syndrome.The endocannabinoid (EC) system (ECS) is known to play a crucial role in energy homeostasis. Regulation by this system takes place at the central level by changing food intake (1), and at the peripheral level by the modification of energy metabolism (2). An overactive ECS plays a crucial role in obesity by increasing food intake (3) and lipogenesis (4), by downregulating catabolic reactions (5,6), and by promoting fat accumulation and alteration of glucose homeostasis. As a consequence, treating obesity by decreasing ECS activity has been considered. A pharmacological approach was developed, leading to the commercialization of an inverse agonist of the cannabinoid receptor type-1 (CB1R) rimonabant. However, this drug was withdrawn from the market because of its undesired central nervous system side effects (7). Meanwhile, the downregulation of ECS tone in peripheral tissues involved in energy homeostasis, either with non-brain-penetrant CB1R blockers, or inhibitors of the biosynthesis of endogenous CB1R agonists, is still considered to be a potential approach to counter the adverse events observed in obesity (8).The ECS is defined as a set of endogenous ligands (ECs), synthesized and degraded by specific enzymes and receptors that are able to bind these molecules. It includes two membrane receptors, CB1R and CB2R, and two main endogenous agonists, N-arachidonoyl-ethanolamine (AEA [or anandamide]) and 2-arachidonoyl-glycerol (2-AG). AEA is typically synthesized by the enzyme N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD), although alternative pathways

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Section: Discussionsupporting

confidence: 90%

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Demizieux

Piscitelli²,

Troy-Fioramonti

et al. 2016

Diabetes

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“…Furthermore, a similar trend was exhibited with DHEA/OEA and percent android fat, indicating that OEA levels have less affi nity for android fat distribution when compared with both AEA and DHEA. It has been identifi ed that the effect of AEA on weight gain can be reduced with the inclusion of dietary EPA and DHA and can reduce visceral fat mass in rats ( 15,30,31 ), thus the observation that DHEA, the NAE-analog of DHA, was correlated with android fat deposition more so than OEA suggests that circulating OEA levels may contribute to a more desirable regional body fat deposition profi le than do other NAEs. Moreover, it was also observed that plasma NAE levels exhibited a moderate direct correlation with carbohydrate oxidation but were inversely correlated with fat oxidation, both resting and postprandial, of which plasma AEA levels showed the strongest correlation.…”

Section: Discussionmentioning

confidence: 99%

Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans

Jones

Lin

Gillingham

et al. 2014

Journal of Lipid Research

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“…Finally, both diets did not alter the animals' performance in the inhibitory avoidance task and, accordingly, no changes in CB 1 receptor and endocannabinoid content In fact, it is well-established that dietary ALA deficiency results in DHA brain deficiency; whereas, the most efficient strategy to increase DHA levels in brain is its dietary intake, more efficiently in the phospholipid form, as in Krill oil (21). In our hands, lifelong administration of n-3-deficient diets impaired short-term memory performance in adult offspring when compared with controls fed a standard diet without inducing any depressive-or anxiety-like symptom.…”

Section: Discussionmentioning

confidence: 92%

“…Because saturated fatty acids are transparent to UV, after derivatization, they were measured as FAMEs by a gas chromatograph (Agilent Model 6890) as described (21).…”

Section: Gc-flame Ionization Detector Analysis Of Fatty Acid Methyl Ementioning

confidence: 99%

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

Zamberletti

Piscitelli²,

Castro

et al. 2017

Journal of Lipid Research

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Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition

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Dietary krill oil increases docosahexaenoic acid and reduces 2-arachidonoylglycerol but not N-acylethanolamine levels in the brain of obese Zucker rats

Cited by 76 publications

References 26 publications

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Early Low-Fat Diet Enriched With Linolenic Acid Reduces Liver Endocannabinoid Tone and Improves Late Glycemic Control After a High-Fat Diet Challenge in Mice

Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

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