Endocannabinoids and Metabolic Disorders

Gatta-Chérifi, Blandine; Cota, Daniela

doi:10.1007/978-3-319-20825-1_13

Cited by 20 publications

(17 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, endocannabinoids (eCBs) play a pivotal role in both homeostatic and rewarding aspects of feeding (Gatta-Cherifi & Cota, 2015). The two primary eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), by interacting with the cannabinoid type-1 receptor (CB1R), increase food intake by modifying the release of orexigenic and anorectic mediators, as well as by reinforcing the hedonic valuation of food (Lau, Cota, Cristino, & Borgland, 2017).…”

mentioning

confidence: 99%

Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

Collu

Scherma

Piscitelli

et al. 2019

Intl J Eating Disorders

View full text Add to dashboard Cite

Objective Despite the growing knowledge on the functional relationship between an altered endocannabinoid (eCB) system and development of anorexia nervosa (AN), to date no studies have investigated the central eCB tone in the activity‐based anorexia (ABA) model that reproduces key aspects of human AN. Method We measured levels of two major eCBs, anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), those of two eCB‐related lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and the cannabinoid type‐1 receptor (CB1R) density in the brain of female ABA rats, focusing on areas involved in homeostatic and rewarding‐related regulation of feeding behavior (i.e., prefrontal cortex, nucleus accumbens, caudato putamen, amygdala, hippocampus and hypothalamus). Analysis was carried out also at the end of recovery from the ABA condition. Results At the end of the ABA induction phase, 2‐AG was significantly decreased in ABA rats in different brain areas but not in the caudato putamen. No changes were detected in AEA levels in any region, whereas the levels of OEA and PEA were decreased exclusively in the hippocampus and hypothalamus. Furthermore, CB1R density was decreased in the dentate gyrus of hippocampus and in the lateral hypothalamus. After recovery, both 2‐AG levels and CB1R density were partially normalized in some areas. In contrast, AEA levels became markedly reduced in all the analyzed areas. Discussion These data demonstrate an altered brain eCB tone in ABA rats, further supporting the involvement of an impaired eCB system in AN pathophysiology that may contribute to the maintenance of some symptomatic aspects of the disease.

show abstract

mentioning

confidence: 99%

Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

Collu

Scherma

Piscitelli

et al. 2019

Intl J Eating Disorders

View full text Add to dashboard Cite

show abstract

“…The CB1R is a typical Gαi/o protein-coupled receptor, and its blockade has functional consequences for intracellular cascades, including elevation of the intracellular cAMP level and attenuation of the [Ca 2+ ] i elevation induced by receptor activation by a CB1R agonist (Chorvat, 2013; Gatta-Cherifi and Cota, 2015). Thus, the effect of TXX-522 on downstream signaling following receptor activation was assayed to further corroborate the efficacy of TXX-522 as a selective CB1R antagonist.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have comprehensively demonstrated the efficacy of globally active first-generation CB1R antagonists in lowering body fat and ameliorating insulin resistance and dyslipidemia (Janero and Makriyannis, 2009; Le Foll et al, 2009; Chen et al, 2013; Lu et al, 2016). Therefore, CB1R has been regarded as an attractive therapeutic target for obesity for the past two decades (Di Marzo et al, 2011; Gatta-Cherifi and Cota, 2015; Kaur et al, 2016; Lu et al, 2016). The first-in-class selective CB1R antagonist and inverse agonist rimonabant (Acomplia; SR141716A), which was successfully approved and introduced into the European market in June of 2006, was anticipated to provide an effective treatment for obesity (Di Marzo, 2008; Sharma et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice

Chen¹,

Shui²,

Liu

et al. 2017

Front. Pharmacol.

View full text Add to dashboard Cite

The clinical development of the first generation of globally active cannabinoid 1 receptor (CB1R) antagonists was suspended because of their adverse neuropsychiatric effects. Selective blockade of peripheral CB1Rs has the potential to provide a viable strategy for the treatment of severe obesity while avoiding these central nervous system side effects. In the current study, a novel compound (TXX-522) was rationally designed based on the parent nucleus of a classical CB1R-selective antagonist/inverse agonist, rimonabant (SR141716A). Docking assays indicate that TXX-522 was bound with the CB1R in a mode similar to that of SR141716A. TXX-522 showed good binding, CB1R-selectivity (over the CB2R), and functional antagonist activities in a range of in vitro molecular and cellular assays. In vivo analysis of the steady state distribution of TXX-522 in the rat brain and blood tissues and the assay of its functional effects on CB1R activity collectively showed that TXX-522 showed minimal brain penetration. Moreover, the in vivo pharmacodynamic study further revealed that TXX-522 had good oral bioavailability and a potent anti-obesity effect, and ameliorated insulin resistance in high-fat diet-induced obese mice. No impact on food intake was observed in this model, confirming the limited brain penetration of this compound. Thus, the current study indicates that TXX-522 is a novel and potent peripherally acting selective CB1R antagonist with the potential to control obesity and related metabolic disorders.

show abstract

“…CRIP1a acts as an endogenous inhibitor and decreases constitutive activity of the CB1 receptor [35] . Essentially, the endocannabinoid system is profoundly involved in the regulation of food intake, metabolism and energy balance [36] and has been the target of numerous pharmacotherapeutic approaches for the treatment of obesity and MS [36] , [37] , making it a likely candidate for the regulation of the metabolic response to WC by miR-219.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

Schroêder

Drori

Ben-Efraim

et al. 2018

Molecular Metabolism

View full text Add to dashboard Cite

Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals.ObjectiveWe attempted to address the issue of individual differences in the response to weight cycling in male mice.MethodsWe first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH) of an additional mouse cohort and performed a full metabolic assessment.ResultsExposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS) animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype.ConclusionsOur results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling.

show abstract

Endocannabinoids and Metabolic Disorders

Cited by 20 publications

References 126 publications

Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice

Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

Contact Info

Product

Resources

About