Central noradrenergic neurotransmission and weight loss following gastric bypass surgery in obese individuals

Objectives: Roux-en Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long term results in weight loss. This is in part expected to result from changes in brain catecholamine transmission mediating appetite and food intake. Although this has already been shown for dopamine, so far no studies on noradrenaline (NA) exist. Therefore this study investigated for the first time whether weight loss after RYGB is associated with alterations in central NA transmission as a key modulator of body weight.Methods: In vivo NA transporter (NAT) availability was determined twice, before and 6 months after RYGB using PET (ECAT EXACT HR+) and NAT-selective S,S-[¹¹C]O-methylreboxetine (MRB; 482±31MBq) in ten highly obese individuals (BMI 47±5 kg/m²; age 44±14 years). Volumes of interest (VOI) were drawn manually on the individual 3T MRI (T1) data using PMOD 3.5 software. Kinetic modeling of regional time activity curves was performed using multilinear reference tissue model 2 (with the occipital cortex as a reference region) to estimate distribution volume ratios (DVR) after co-registration of PET data with MRI-VOI set. Results: All participants responded on RYGB surgery with a change in BMI from pre-surgery (pre) to 6-months follow up visit (post, BMI 34.9±4.6 kg/m²) of 12.0±3.5 kg/m² and a reduction in body weight (BW), pre 134.6±19.7 kg, post 101.4±11.5 kg, ΔBW= -35.4±11.7 kg, p<0.001). This change in BMI (ΔBMI) was positively associated with a change of DVR (pre-post) in the hypothalamus with borderline significance (r= 0.65; p=0.06), but there was no other trends towards an association between ΔBMI/ ΔBW and changes in DVR in other brain regions (e.g. in the insula pre 1.2 ± 0.06, post 1.2 ± 0.09; p=0.22 and the locus coeruleus pre 1.4±1.2, post 1.3±1.3; p=0.16). Furthermore, we found a significant positive correlation between the change in BMI and the pre DVR in hypothalamus (r=0.78; p=0.01) and a tendency to a significant association for the hippocampus (r=-0.64; p=0.06). Conclusion: Yet, there is no marked association between changes in central NAT availability and weight loss after RYGB surgery. However, the high correlation coefficients between preoperative NAT values and the changes in BW within 6 months follow up indicate that 1) NA transmission has influence on BMI/BW and 2) NAT availability can predict long-term outcome after RYGB but both assumptions need confirmation in in vivo PET studies on NA transmission with a larger cohort size.