Brain dopamine D1 receptor in human gastric bypass responders versus non-responders (Prof. Dr. Swen Hesse)
In diesem Projekt untersuchen die Wissenschaftler/innen untersucht mittels PET/MRI Messungen und einem D1R-selektiven Radioliganden die Verfügbarkeit von D1R in Patienten mit einem Roux-Y-Magenbypass.
Laufzeit: 01.11.2017 – 30.04.2020
Beschreibung des Forschungsprojekts
Peripheral signals influence not just homeostatic, but also hedonic aspects of feeding via gut-brain pathways, and thus play an important role in the motivation to eat. A key structure at the interface between cortical (i.e. prefrontal) networks and afferent information is the central dopamine (DA) system. It integrates sensory infor-mation, which is processed in mesolimbic and nigrostriatal reward-related circuits. Recent evidence suggests that these signals contribute to changes in striatal DA transmission in obesity resulting in altered perception of the rewarding properties of dietary fat intake after bariatric (Roux-en-Y gastric bypass, RYGB) surgery. According to animal models, activation of striatal DA D1 receptor (D1R) can be assigned as crucial for sustained surgically-induced weight loss, but this has not been investigated in humans. The proposed study is the first, which directly measures in vivo D1R availability using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) and the D1R-selective radioligand [11C]SCH23390 in patients who underwent RYGB surgery. To investigate its role on surgical outcome, brain D1R availability will be measured in patients that sustainably respond to RYGB treatment (>70% excess weight loss, EWL, maintained for at least 2 years after surgery) and in patients with poor treatment response (<30% EWL 2 years after surgery). To additionally test for feeding-induced DA release, patients will undergo two scans, one following a 16-h fast and the other after consumption of a standardized favorable meal. Based on our preclinical results, we hypothesize that responders have a significantly higher D1R activity in the dorsal striatum (as a part of the nigrostriatal system) together with increased reward sensitivity and salient network activation compared with non-responders. If confirmed, study results will encourage new strategies targeted at improving DA function in the treatment of obesity as a subtype of reward deficiency.
