Abstract
1048
Introduction: The brain neurotransmitters serotonin and noradrenaline are both implicated in the regulation of appetite and energy balance. Alterations of these systems, i.e. in key areas of feeding control such as the hypothalamus or the dorsal raphe nucleus (DRN), lead to eating disorders and obesity; however, the underlying mechanisms are not fully explored yet. Here, we propose a model of body mass index (BMI)-related changes of SERT and NAT together with post-interventional (diet, Roux-Y-gastric bypass surgery, RYGB) data.
Methods: PET was performed in non-depressed individuals with obesity twice prior and after 6 months following dietary or RYGB intervention using SERT-selective 11C-DASB (n=30 diet, BMI 41.3±4.9 kg/m2, age 37±10 years, 22 females; n=13 RYGB, BMI 45.0±3.9 kg/m2, age 45±12 years, 7 females) or 11C-MRB (n=10 diet, BMI 42.4±3.6 kg/m2, age 34±9 years, 4 females; n=9 RYGB, BMI 46.9±4.9 kg/m2, age 46±13 years, 7 females) to obtain SERT/NAT binding potential BPND (applying multilinear reference tissue modelling with two parameters) of the hypothalamus and the DRN (individually defined on coregistered MRI) as the primary outcome measure compared with the baseline and 6-months follow-up data of normal-weight (NW), healthy controls (n=15 11C-DASB, BMI 22.5±2.5 kg/m2, age 36±7 years, 10 females; n=10 11C-MRB, BMI 23.9±2.5 kg/m2, age 33±10 years, 4 females).
Results: At baseline, SERT BPND in the DRN was highest in the diet group (NW 2.99±0.7 vs. diet 3.63±0.9 vs. RYGB 3.15±2.0; ANOVA p=0.19). Post-diet data showed no changes in SERT BPND (DRN) while average change of BMI was modest (mean -2.8 kg/m2 or -6.8%; p=0.01). SERT BPND increased after RYGB (follow-up: 3.45±0.2; p=0.1) together with a highly significant decrease of BMI (mean -12.4 kg/m2 or -26.7%; p<0.0001). NAT BPND in the hypothalamus decreased with increasing BMI (NW 0.53±0.1 vs. diet 0.43±0.2 vs. RYGB 0.44±0.1, ANOVA p=0.26) forming a U-shaped relationship between NAT and BMI (R2=0.2; Figure). As predicted from the baseline measures, NAT BPND increased slightly after diet (0.44±0.2; n.s.) and decreased after RYGB (follow-up: 0.30±0.2; p=0.15; Figure). Both BMI and BPND remained stable in NW. Conclusion: Taken together, our findings suggest a dynamic relationship between both monoamine systems and markers of obesity during the development of obesity, possibly based on tonus shifts, processes of neuroplasticity, or different endophenotypes in individuals with moderate obesity and severe obesity. Specifically, our data indicate a model of curvilinear and inverse curvilinear relationship of the respective transporters related to the BMI in regions relevant for feeding control. If confirmed in larger series and further related to the individual endocrine, metabolic and behavioral factors, such findings may point to the use of one or both transporters as PET biomarker for treatment decision, course monitoring and for the prediction of treatment success. Acknowledgements: The work was supported by the Federal Ministry of Education and Research, Germany, FKZ: 01E01001
