DRD2 and ANKK1 genes polymorphism in overweight and obese women and comparsion of serum levels of BDNF, leptin and insulin .in women with different severity of hedonic eating

Abstract

Abstract Introduction: Obesity is a multifactorial disease, caused by an imbalance between energy intake and energy expenditure. In general, food intake is regulated by two complementary drives: the homeostatic and hedonic pathways. The homeostatic pathway controls energy balance by increasing the motivation to eat following depletion of energy stores. In contrast, hedonic pathway can override the homeostatic pathway during periods of relative energy abundance by increasing the desire to consume highly palatable foods. Hedonic eating, regulated by the mesolimbic dopamine system, is in fact, due to the pleasure of the reward value of palatable foods and is considered an important factor for obesity. Therefore, dopamine receptor polymorphisms, especially variants in the genes regulating the D2 receptor including ANKK1 and DRD2 are prime candidates for assessing the individual differences in hedonic eating. In addition, there are some appetite regulatory substances including insulin, leptin, and brain-derived neurotrophic factor (BDNF) that play roles in the regulation of both homeostatic and hedonic eating. This study was carried out to investigate the ANKK1 and DRD2 gene polymorphisms and to evaluate the association between these polymorphisms and hedonic eating and food craving. In addition, the levels of some appetite regulatory substances were compared in participants with high and low hedonic hunger for the first time. Methods: In the present descriptive-analytical research, 413 overweight and obese women aged between 19-49 years were studied. All participants’ anthropometric indices were measured. The Power of food scale-Persian (PFS-P), Food craving inventory-Persian (FCI-P), International Physical Activity Questionnaire (IPAQ), and a demographic questionnaire were completed for all participants. The attendants were genotyped for ANKK1 (CC, CT and TT) and DRD2 (Ins/Ins, Ins/Del and Del/Del) polymorphisms using restriction fragment length polymorphism (RFLP) -PCR. Based on the PFS scores, the participants were divided into two groups: low and high hedonic hunger and 45 women with high and45 women low hedonic eating scores were randomly selected and serum levels of fasting blood sugar (FBS), insulin, leptin, and brain-derived neurotrophic factor (BDNF) were determined in the two groups. Additionally, the levels of insulin, leptin, and BDNF were compared between the CC and CT+TT groups as well as between the Ins/Ins and Ins/Del+ Del/Del groups. Data were analyzed using descriptive analysis tests, independent samples t-test, Chi-square, and ANCOVA. Results: The participants’ mean age and BMI were 37.49±8.68 years and 33.06±5.31 kg/m2, respectively. The majority (91.5%) of the participant were inactive, about 7.9% were minimally active, and 0.7% were highly active. The mean of hedonic eating and food craving scores in the total sample was 3.23±0.80 and 2.66±0.51, respectively. Hedonic eating and food craving were significantly different in overweight women compared with obese ones (P<0.001). ANKK1 genotyping identified 265 (64.16%) participants as CC (A2A2) genotype, 132 (31.96%) as CT (A1A2) genotype and 16 (3.87%) as TT (A1A1) genotype. In addition, DRD2 genotyping showed 229 (55.37%) participants as Ins/Ins genotype, 158(38.29%) as Ins/Del genotype, and 26 (6.34%) as Del/Del genotype. There were no significant differences in genotype frequencies of ANKK1 and DRD2 gene polymorphisms between the overweight and obese women. Significant associations were observed between ANKK1 genotypes and hedonic eating and food craving. However, DRD2 genotypes were not significantly associated with hedonic eating and food craving. Additionally, the participants in the high hedonic group had higher levels of insulin and leptin than the low hedonic group. In contrast, a significantly higher level of BDNF was observed in the low hedonic group. No significant differences were observed between the CC and CT+TT as wel as between the Ins/Ins and Ins/Del+ Del/Del, regarding serum levels of insulin, leptin, and BDNF (P>0.05)Conclusion: Our findings showed that hedonic eating and food craving were significantly higher in overweight women than obese one. ANKK1 polymorphisms was significantly associated with hedonic eating and food craving. The levels of insulin and leptin were significantly higher in women with high hedonic eating, compared to low hedonic ones. In contrast, the mean level of serum BDNF was significantly lower in the high hedonic group.