The cDNA 385C to A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) is associated with overweight/obesity but not with binge eating disorder in overweight/obese women

Monteleone, Palmiero; Tortorella, Alfonso; Martiadis, Vassilis; Filippo, Clara Di; Canestrelli, Benedetta; Maj, Mario

doi:10.1016/j.psyneuen.2008.01.004

Cited by 58 publications

(46 citation statements)

References 17 publications

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“…8 Sipe et al 9 have shown that the homozygous FAAH 385 A/A genotype was associated with overweight and obesity. Monteleone et al 10 confirmed previously published significant overrepresentations of the FAAH 385A allele in overweight/obese subjects. Considering the evidence that the endogenous cannabinoid system has a role in metabolic aspects of body weight, 11 the aim of our study was to investigate the relationship between the polymorphism (cDNA 385 C-4A) of the FAAH gene and visfatin levels in obese women.…”

Section: Introductionsupporting

confidence: 77%

C358A missense polymorphism of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and visfatin levels in obese females

et al. 2010

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Background: Recently, it has been shown that the polymorphism 385 C/A of FAAH (fatty acid amide hydrolase) was associated with overweight and obesity. Visfatin has been identified as a protein expressed in visceral adipose tissue with contradictory functions in glucose metabolism. Objective: The aim of our study was to investigate the relationship between polymorphism (cDNA 385 C-4A) of the FAAH gene and visfatin levels in obese women. Design: A population of 143 females with obesity was analyzed. Indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure and serial assessment of nutritional intake with 3-day written food records and biochemical analysis (lipid profile, visfatin, insulin, C-reactive protein and homeostasis model assessment for insulin sensitivity (HOMA)) were performed. Results: Ninety-four patients (65.7%) had the genotype C358C (wild-type group) and 49 (34.3%) patients had the genotype C358A (mutant type group). No differences were detected between groups in anthropometric parameters and dietary intakes. Insulin (15.6±7.6 vs 14.1±10.1 mUI l À1 ; Po0.05), glucose (101.2±21.9 vs 92.3±10.5 mg per 100 ml; Po0.05) and HOMA values (3.96 ± 2.3 vs 3.15 ± 2.8; Po0.05) were higher in the wild type-group than in the mutant type group. Visfatin levels were lower in the wild-type group than in the mutant type group (47.83±57.5 vs 65.71±55 ng ml À1 ; Po0.05). Conclusion:The novel finding of this study is the association of the mutant type group A358C of FAAH with lower glucose, insulin and HOMA levels than of the wild-type group with higher visfatin levels.

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Section: Introductionsupporting

confidence: 77%

C358A missense polymorphism of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and visfatin levels in obese females

et al. 2010

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“…Mice lacking FAAH (FAAH −/− mice) have increased body weight after 12 wk of HFD feeding, independent of food intake (7) and decreased energy expenditure (EE) (15). Furthermore, SNPs in the FAAH gene correlate with obesity in humans (16,17).NAEs are lipid-signaling molecules that have diverse physiological effects. Anandamide (AEA), an endocannabinoid and an endogenous ligand of CB1, is the most well-studied NAE (11).…”

mentioning

confidence: 99%

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confidence: 99%

Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism

Brown

Gillum

Lee

et al. 2012

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

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Fatty acid amide hydrolase (FAAH) knockout mice are prone to excess energy storage and adiposity, whereas mutations in FAAH are associated with obesity in humans. However, the molecular mechanism by which FAAH affects energy expenditure (EE) remains unknown. Here we show that reduced energy expenditure in FAAH −/− mice could be attributed to decreased circulating triiodothyronine and thyroxine concentrations secondary to reduced mRNA expression of both pituitary thyroid-stimulating hormone and hypothalamic thyrotropin-releasing hormone. These reductions in the hypothalamic-pituitary-thyroid axis were associated with activation of hypothalamic peroxisome proliferating-activated receptor γ (PPARγ), and increased hypothalamic deiodinase 2 expression. Infusion of NAEs (anandamide and palmitoylethanolamide) recapitulated increases in PPARγ-mediated decreases in EE. FAAH −/− mice were also prone to diet-induced hepatic insulin resistance, which could be attributed to increased hepatic diacylglycerol content and protein kinase Cε activation. Our data indicate that FAAH deletion, and the resulting increases in NAEs, predispose mice to ectopic lipid storage and hepatic insulin resistance by promoting centrally mediated hypothyroidism. NAPEs) and N-acylethanolamines (NAEs) are nutrient-regulated lipokines that affect energy homeostasis through regulation of satiety and energy storage, selectively increasing in abundance with high-fat diet (HFD) feeding (1-7). NAPEs are hydrolyzed to produce diverse NAE species, which act as ligands for cannabinoid receptor 1 (CB1), G protein-coupled receptor 119 (GPR119), GPR55, peroxisome proliferating-activated receptor α (PPARα), and transient receptor potential cation channel subfamily V member 1 to affect appetite, gut hormone release, anxiety, and inflammation (8-12). Fatty acid amide hydrolase (FAAH) is the major enzyme responsible for the degradation of NAEs. An integral membrane protein, FAAH is expressed predominantly in the brain, liver, kidney, and intestine (13,14). Mice lacking FAAH (FAAH −/− mice) have increased body weight after 12 wk of HFD feeding, independent of food intake (7) and decreased energy expenditure (EE) (15). Furthermore, SNPs in the FAAH gene correlate with obesity in humans (16,17).NAEs are lipid-signaling molecules that have diverse physiological effects. Anandamide (AEA), an endocannabinoid and an endogenous ligand of CB1, is the most well-studied NAE (11). Inhibition of CB1 promotes EE, leading to decreased body weight in HFD-fed mice (18). In addition, treatment with the CB1 inhibitor rimonabant increases oxygen consumption in isolated soleus muscle of obese mice (5).Because FAAH is expressed in metabolically active tissues and may be a genetic cause of obesity in humans, we investigated EE and tissue-specific insulin sensitivity in FAAH −/− and FAAH +/+ mice. To do so, we measured the expression of genes and hormones known to regulate EE, including PPARγ, proopiomelanocortin (POMC), and thyroid hormones. Here we show that FAAH regulates EE via the ac...

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“…In this respect, have been studied CNR1 and CNR2 (the genes encoding cannabinoid CB1Rs and CB2Rs, respectively), as well as the genes encoding the main enzyme responsible in the degradation of AEA (FAAH), NAAA (N-Acylethanolamine-hydrolyzing acid amidase [88][89][90][91][92][93].…”

Section: Cannabinoids and Eating Disordersmentioning

confidence: 99%

“…Another study in 115 overweight/obese subjects with bingeeating disorder, 74 non-binge-eating disorder patients with obesity and 110 normal weight healthy controls investigated one of these FAAH polymorphisms, previously implicated in obesity in bingeeating disorder, and reporting a lack of association [90] and in a more recent article these authors studied the association of this FAAH polymorphism and the CNR1 polymorphism in both AN and BN, in 134 patients with AN, 180 patients with BN and 148 normal weight healthy controls [91]. The authors found a significant increase in the frequency of both polymorphisms in AN and BN patients, a result in sharp contrast with the previous findings by Muller et al [89] that showed a lack of association of these polymorphisms with AN.…”

Section: Cannabinoids and Eating Disordersmentioning

confidence: 99%

The role of endocannabinoids in the control of eating disorders

Milano¹,

Tecce²,

Capasso³

2017

Dis Disord

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Eating Disorder (ED) is a syndrome characterized by persistent alteration of eating behavior and the conditions that cause an insufficient ingestion and/or adsorption of foods. There are three different ED diseases: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorders (BED). ED are complex conditions that arise from a combination of long-standing behavioral, emotional, psychological, interpersonal, and social factors. The neuronal circuits that control the ingestion of food are mainly related to catecholaminergic, serotoninergic and peptidergic systems. In this respect, while serotonin, dopamine and prostaglandin promote the ingestion of food, by contrast, neuropeptide Y, norepinephrine, GABA and opioid peptides inhibit food ingestion thus causing the occurrence of ED. The drugs mainly used in the treatment of ED are antidepressants such as selective serotonin reuptake inhibitors and tricyclic antidepressant. Additionally, mood stabilizers (lithium), anxiolytics, serotonin and noradrenalin reuptake inhibitors and antipsychotic drugs are often used in the treatment of ED.Several studies indicate that the endocannabinoid system is involved in ED supporting the idea that the cannabinoid signaling system is a key modulatory element in the activity in the brain area associated with ED.

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The cDNA 385C to A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) is associated with overweight/obesity but not with binge eating disorder in overweight/obese women

Cited by 58 publications

References 17 publications

C358A missense polymorphism of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and visfatin levels in obese females

C358A missense polymorphism of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and visfatin levels in obese females

Fatty acid amide hydrolase ablation promotes ectopic lipid storage and insulin resistance due to centrally mediated hypothyroidism

The role of endocannabinoids in the control of eating disorders

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