FAAH gene polymorphisms, plasma levels of endocannabinoids and their relation with appetite regulatory substances in overweight and obese women with and without binge eating disorder

Abstract

Introduction: BED is the most common eating disorders and is associated with repetitive periods of excessive food intake and loss of control but without purging behaviors. The endocannabinoid system is one of the important systems that play an important role in regulating appetite and food intake and probably eating disorders. A single nucleotide polymorphism (cDNA 385C to A) of the gene coding for fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, has been found to be associated with obesity and eating disorders. Additionally, some appetite regulators including leptin, insulin, and orexin A, are involved in the synthesis and release of endocannabinoids, and as a result, changes in their levels can lead to overeating. The aim of this study was to investigate the polymorphisms of FAAH gene, plasma levels of endocannabinoids and their relationship with appetite regulatory substances in overweight and obese women with and without binge eating disorder. Methods: In the present descriptive-analytical research, 180 overweight and obese women aged between 19-49 years were studied. All participants’ anthropometric indices were measured. Binge Eating Scale (BES), International Physical Activity Questionnaire (IPAQ), Food Frequency Questionnaire (FFQ) and a demographic questionnaire were completed for all participants. The BES was designed as a measure of diagnosis and severity of BE and its scores are summed and range from 0 to 46, with BES representing none (≤17 total score), moderate (18–26), and severe (>27) binge eating problems. The attendants were genotyped for FAAH (CC, CA and AA) polymorphisms using amplification refractory mutation system (ARMs) -PCR. The levels of anadamide (AEA), 2-arachidonoylglycerol (2-AG), leptin, insulin, and orexin-A was measured by ELISA kits. Results: The mean age and body mass index of the participants were 34.2 ± 8.27 years and 32.54 ± 3.73 kg/m2 respectively. About 41.6% of individuals were diagnosied as having binge eating disorde score of binge eating disorder in women was 24.98. The binge eating disorder mean score in obese women was significantly higher than overweight women (P <0.05). Regarding the FAAH genotype, 68.34% of the participants had CC genotype and 31.66% of them had CA+ AA genotype. Also, the frequency of allele A in women with binge eating disorder (24.65%) was higher than women without binge eating disorder (14.3%), but these differences were not statistically significant between two groups (P> 0.05). In addition, binge eating disorder women exhibited significantly higher levels of AEA, 2-AG, leptin, and insulin compared to non- BED women (P< 0.05). There was a significant difference between CA + AA and CC groups in terms of AEA and 2-AG levels (P <0.05); however, no significant differences concerning leptin, insulin, and orexin levels between the two groups were observed (P >0.05). Moreover, 2-AG showed a significant relationship with insulin and leptin and AEA showed a significant relationship with leptin (P< 0.05). With regard to r, of which 27.2% had moderate and 14/4% had severe binge eating disorder. The mean the relationship between energy, macronutrients and endocannabinoids, it was observed that energy, fat and carbohydrate were significantly associated with 2- AG and energy and fat were significantly associated with AEA (P< 0.05). Conclusion: About half of the participants were diagnoised as having BED. The levels of studied endocannabinoids and also leptin, insulin levels were significantly higher in women with BED. Key words: binge eating disorder; obesity; endocannabinoids; leptin; insulin; orexin- A