Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

Monteleone, Palmiero; Matías, Isabelle; Martiadis, Vassilis; Petrocellis, Luciano De; Maj, Mario; Marzo, Vincenzo Di

doi:10.1038/sj.npp.1300695

Cited by 243 publications

(174 citation statements)

References 27 publications

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“…In this direction, Endogenous cannabinoids in the brain and peripheral tissues I Matias et al data from our laboratory indicate that the blood levels of endocannabinoids in anorexic women are significantly higher than in healthy women, and inversely correlated with blood leptin levels. 35 Furthermore, obese women with binge eating disorder, despite the very high levels of leptin, also possess higher blood endocannabinoid levels, which in this case are positively correlated with body fat mass, thus suggesting that one type of control on the endocannabinoid system may prevail over another during some eating disorders. 35 Indeed, the picture of a general hyperactivity of the endocannabinoid system during obesity, at both the central and peripheral levels, is emerging from recent studies.…”

Section: Discussionmentioning

confidence: 87%

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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Section: Discussionmentioning

confidence: 87%

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

2006

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“…36,37 Physiologically, this can promote feelings of being unable to control one's response to eating and food. 38,39 Subsequently, this may increase UE, EE and, in some populations, decrease CR. Clearly, more research is needed in this area.…”

Section: Discussionmentioning

confidence: 99%

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants

et al. 2009

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Background:The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale that measures three domains of eating behavior: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE). Objectives: To assess the factor structure and reliability of TFEQ-R21 (and if necessary, refine the structure) in diverse populations of obese and non-obese individuals. Design: Data were obtained from obese adults in a United States/Canadian clinical trial (n ¼ 1741), and overweight, obese and normal weight adults in a US web-based survey (n ¼ 1275). Confirmatory factor analyses were employed to investigate the structure of TFEQ-R21 using baseline data from the clinical trial. The model was refined to obtain adequate fit and internal consistency. The refined model was then tested using the web-based data. Relationships between TFEQ domains and body mass index (BMI) were examined in both populations. Results: Clinical data indicated that TFEQ-R21 needed refinement. Three items were removed from the CR domain, producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI) ¼ 0.91). Testing TFEQ-R18V2 in the web-based sample supported the revised structure (CFI ¼ 0.96; Cronbach's coefficient a of 0.78-0.94). Associations with BMI were small. In the clinical study, the CR domain showed a significant and negative association with BMI. On the basis of the web-based survey, it was shown that the relationship between BMI and CR is population-dependent (obese versus non-obese, healthy versus diabetics). Conclusions: In two independent datasets, the TFEQ-R18V2 showed robust factor structure and good reliability. It may provide a useful tool for characterizing UE, CR and EE.

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“…S1B). Quantitative analysis using liquid chromatography-multiple reaction monitoring (LC-MRM) measurements revealed that only 23.6 ± 4.8% (n = 6) of the exogenously applied dose of lipophilic AEA reached the lungs via the tubes of the perfusion system of the IPL; these data indicate that AEA evoked pulmonary vasoconstriction at concentrations that have been measured in the human blood (13,14). The effect of AEA was specific because no response was observed upon perfusion with the solvent ethanol ( Fig.…”

Section: Resultsmentioning

confidence: 87%

Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction

Wenzel

Matthey²,

Bîndilă

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Endocannabinoids are important regulators of organ homeostasis. Although their role in systemic vasculature has been extensively studied, their impact on pulmonary vessels remains less clear. Herein, we show that the endocannabinoid anandamide (AEA) is a key mediator of hypoxic pulmonary vasoconstriction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites. This is underscored by the prominent vasoconstrictive effect of AEA on pulmonary arteries and strongly reduced HPV in FAAH −/− mice and wild-type mice upon pharmacological treatment with FAAH inhibitor URB597. In addition, mass spectrometry measurements revealed a clear increase of AEA and the FAAH-dependent metabolite arachidonic acid in hypoxic lungs of wild-type mice. We have identified pulmonary vascular smooth muscle cells as the source responsible for hypoxia-induced AEA generation. Moreover, either FAAH −/− mice or wild-type mice treated with FAAH inhibitor URB597 are protected against hypoxia-induced pulmonary hypertension and the concomitant vascular remodeling in the lung. Thus, the AEA/ FAAH pathway is an important mediator of HPV and is involved in the generation of pulmonary hypertension. pulmonary vascular tone | cannabinoid E ndocannabinoids have been shown to induce vasorelaxation in systemic vessels which is primarily mediated by the specific cannabinoid 1 and 2 (CB1/CB2) and also other G protein-coupled receptors (e.g., non-CB1/CB2 receptors) (1, 2). Based on these results, especially CB1 receptors have been proposed as promising therapeutic targets for the treatment of arterial hypertension (2). Endocannabinoids are also known to potentially act via their intracellular enzymatic metabolization by the fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) to (vaso)active intermediates (3, 4), but these pathways are considered less important for the regulation of vascular tone in systemic vessels.Pulmonary arteries are unique because of their prominent vasoconstriction in response to hypoxia. Hypoxic vasoconstriction is responsible for adapting perfusion to ventilation in the lungs and therefore also plays an important role in pathophysiological situations characterized by a high ventilation/perfusion mismatch such as acute lung injury or liver cirrhosis (5, 6). In addition, this mechanism potentially contributes to the onset of pulmonary hypertension in response to hypoxia occurring in high altitude or in various respiratory diseases such as chronic obstructive pulmonary disease or fibrosis (7-9). Pulmonary arterial smooth muscle cells are suggested to play a major role in hypoxic vasoconstriction (10), but the precise mechanisms and the underlying signals are still not well understood. Earlier experimental evidence suggested that the endocannabinoid anandamide (AEA) can either enhance (11) or reduce (12) pulmonary arterial tone, and this prompted us to reexplore the role of endocannabinoids in basic physiological and pathophysiological responses of pulmonary arteries using experimental in vitro, ex vivo, and in viv...

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Blood Levels of the Endocannabinoid Anandamide are Increased in Anorexia Nervosa and in Binge-Eating Disorder, but not in Bulimia Nervosa

Cited by 243 publications

References 27 publications

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

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

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants

Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction

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