Griebsch Nora-Isabell, Kern Johanna, Hansen Jonas, Rullmann Michael, Luthardt Julia, Helfmeyer Stephanie, Dekorsy Franziska J, Soeder Marvin, Hankir Mohammed K, Zientek Franziska, Becker Georg-Alexander, Patt Marianne, Meyer Philipp M, Dietrich Arne, Blüher Matthias, Ding Yu-Shin, Hilbert Anja, Sabri Osama, Hesse Swen
Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig, Germany.
Integrated Research and Treatment Center Adiposity Diseases, 04103 Leipzig, Germany.
Brain Sci. 2022 Oct 26;12(11):1437. doi: 10.3390/brainsci12111437.
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
血清素（5-羟色胺，5-HT）以及去甲肾上腺素（NA）是包括食欲控制在内的各种基本脑功能的关键调节因子。虽然改变脑血清素能信号的操作明显影响体重，但将5-HT转运体和NA转运体（分别为5-HTT和NAT）作为人类肥胖主要药物治疗靶点的研究尚无定论。本正电子发射断层扫描（PET）研究的目的是调查在6个月的饮食干预或Roux-en-Y胃旁路术（RYGB）后，这些中枢转运体如何与体重变化相关联，以评估5-HTT以及NAT的可用性是否能够预测体重减轻以及治疗效果。研究人群包括两个研究队列，一个使用5-HTT选择性放射性示踪剂[11C]DASB来测量5-HTT的可用性，另一个使用NAT选择性放射性示踪剂[11C]MRB来评估NAT的可用性。每组包括非肥胖健康参与者、遵循保守饮食计划（节食）的重度肥胖患者（体重指数，BMI，>35 kg/m2）以及在6个月随访期内接受RYGB手术的患者。总体而言，BMI的变化与5-HTT和NAT可用性的变化均无关联，而干预前中缝背核（DRN）中的5-HTT可用性与RYGB手术后BMI的显著降低相关，与节食后BMI的适度降低呈负相关。综上所述，我们的研究数据表明，5-HTT和NAT参与了肥胖的发病机制，并且有可能作为治疗结果的预测指标。
