Comparison of endocannabinoids levels, FAAH gene polymorphisms, and appetite regulatory substances in women with and without binge eating disorder: a cross- sectional study

Abstract

Binge eating disorder (BED) is known as the most common eating disorder with both psychosocial and biological factors involved. In this regard, there is a need to recognize probable disturbances in substances involved in food intake regulation in BED. In this study, we hypothesized that the levels of endocannabinoids, fatty acid amid hydrolase (FAAH) gene polymorphisms, and appetite regulatory substances are different in overweight and obese women with and without BED. A Binge Eating Scale was used to estimate the prevalence of BED in 180 women classified as overweight or obese. The levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), leptin, insulin, and orexin-A were measured by enzyme-linked immunosorbent assay kits. The subjects were genotyped for polymorphisms of FAAH gene using amplification refractory mutation system–polymerase chain reaction. Data were analyzed using SPSS software. About 41.6% (n = 75) of the subjects were diagnosed with BED. Women with BED exhibited significantly higher levels of AEA, 2-AG, leptin, and insulin compared to non-BED women (P < .05). Binary logistic regression analysis also showed that AEA, leptin, and insulin were the predictors of having BED after adjusting for body mass index (P < .05). In addition, the frequency of A allele of FAAH gene was higher in women with BED compared to women without BED; however, there were no significant differences between these 2 groups (P = .08). These results supported our hypothesis in the cases of AEA, 2-AG, leptin, and insulin but not orexin and FAAH gene polymorphisms. The findings of the current study provide further evidence concerning the role of these substances in BED.

Introduction

Global reports indicate that overweight and obesity are 2 of the most important public health problems in all age groups throughout the world [1]. Although obesity is a multifactorial metabolic disorder, its major reasons have not been well recognized yet. However, the unusual motivation leading to eating beyond satiety is still a critical problem that usually results in obesity [2].

Obesity and its complications are regarded as the medical comorbidities that are frequently seen in binge eating disorder (BED) [3]. Among eating disorders, BED is known as the most common one, which is associated with repetitive periods of excessive food intake and loss of control but without purging behaviors [4]. In the Appendix of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, of the American Psychiatric Association, BED falls into the Eating Disorder Not Otherwise Specified category [5]. In individuals with obesity, BED is overrepresented and might be considered as one of the contributing factors to their weight gain [6]. Throughout the life cycle, the BED prevalence rate in community samples of individuals 18 years and older is 3.5%, with the rates much higher (6.2%) in women between 18 and 24 years of age. It also seems to be more prevalent among overweight and obese samples (30%) compared to the general population [7]. The present increase in obesity and recent BED rate that likely contributes to obesity is an important factor that must be understood [8].

It is generally believed that eating disorders have a multifactorial and complex etiopathogenesis, with both psychosocial and biological factors involved [9]. The endogenous cannabinoids (eg, anandamide [AEA] and 2-arachidonoyl glycerol [2-AG]) have been shown to control food intake in both humans and animals, in addition to modifying eating behavior, which demonstrates that endocannabinoid system alterations could be engaged in the eating disorders pathophysiology [10,11]. Also, polymorphisms of the fatty acid amid hydrolase (FAAH) gene, the main deactivating enzyme of anadamide, have previously been shown to increase the biological susceptibility of eating disorders [12,13]. In fact, the FAAH gene disruption significantly raises the levels of endogenous fatty acid amides in the central nervous system, which result in appetite modulation.

Moreover, based on the reported relationship of the endocannabinoids with endogenous leptin and because of the previously explained effects of long-term food deficit on these factors in brain, it seems reasonable that leptin is also involved in the EDs pathophysiology [14,15].

In different studies, a higher prevalence of BED has been documented in overweight and young patients with type 2 diabetes [16,17]. Additionally, BED is associated with insufficient glycemic control as well as more adverse diabetic complications among adolescents with type 1 diabetes [1]. Obesity-induced insulin resistance can cause changes in the suppressive effects of insulin on brain reward processing regions, which consequently result in overeating and subsequent EDs [18,19].

Approximately 20 years ago, a group of neuropeptides, known as orexins (orexin-A and orexin-B), was discovered within the lateral hypothalamus [20]. Accordingly, orexins have been shown to have a positive role in food intake, mainly in palatable foods intake. Consequently, it is highly possible that these neurons engage in binge eating that includes a hedonic control of food intake [21].

To manage binge eating behavior efficiently, it is required to further examine the substances and genes associated with this behavior. In this study, we assessed the hypothesis that the levels of endocannabinoids, FAAH gene polymorphisms, and appetite regulatory substances would be different in women who are overweight and obese with BEDs. Our specific objectives were to evaluate the BED prevalence in the participants included and to compare the levels of AEA, 2-AG, leptin, insulin, orexin A, and the genotypes of FAAH gene in women with and without BED.