Hesse Swen, Rullmann Michael, Luthardt Julia, Winter Karsten, Hankir Mohammed K, Becker Georg-Alexander, Zientek Franziska, Reissig Georg, Regenthal Ralf, Drabe Mandy, Schinke Christian, Bresch Anke, Arelin Katrin, Lobsien Donald, Patt Marianne, Meyer Philipp M, Fasshauer Mathias, Fenske Wiebke K, Blüher Matthias, Stumvoll Michael, Sabri Osama
Department of Nuclear Medicine, University of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany.
Integrated Research and Treatment Centre Adiposity Diseases Leipzig, Leipzig, Germany.
Eur J Nucl Med Mol Imaging. 2016 Jun;43(6):1096-104. doi: 10.1007/s00259-015-3243-y. Epub 2015 Nov 18.
The role of the central serotonin (5-hydroxytryptamine, 5-HT) system in feeding has been extensively studied in animals with the 5-HT family of transporters (5-HTT) being identified as key molecules in the regulation of satiety and body weight. Aberrant 5-HT transmission has been implicated in the pathogenesis of human obesity by in vivo positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. However, results obtained thus far from studies of central 5-HTT availability have been inconsistent, which is thought to be brought about mainly by the low number of individuals with a high body mass index (BMI) previously used. The aim of this study was therefore to assess 5-HTT availability in the brains of highly obese otherwise healthy individuals compared with non-obese healthy controls.
We performed PET using the 5-HTT selective radiotracer [(11)C] DASB on 30 highly obese (BMI range between 35 and 55 kg/m(2)) and 15 age- and sex-matched non-obese volunteers (BMI range between 19 and 27 kg/m(2)) in a cross-sectional study design. The 5-HTT binding potential (BPND) was used as the outcome parameter.
On a group level, there was no significant difference in 5-HTT BPND in various cortical and subcortical regions in individuals with the highest BMI compared with non-obese controls, while statistical models showed minor effects of age, sex, and the degree of depression on 5-HTT BPND.
The overall finding of a lack of significantly altered 5-HTT availability together with its high variance in obese individuals justifies the investigation of individual behavioral responses to external and internal cues which may further define distinct phenotypes and subgroups in human obesity.
中枢5-羟色胺（5-羟色胺，5-HT）系统在进食中的作用已在动物中得到广泛研究，5-HT转运体家族（5-HTT）被确定为饱腹感和体重调节的关键分子。体内正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）成像技术表明，5-HT异常传递与人类肥胖的发病机制有关。然而，迄今为止，关于中枢5-HTT可用性的研究结果并不一致，这主要被认为是由于之前研究中使用的高体重指数（BMI）个体数量较少所致。因此，本研究的目的是评估极度肥胖但健康的个体与非肥胖健康对照者大脑中5-HTT的可用性。
在一项横断面研究设计中，我们使用5-HTT选择性放射性示踪剂[(11)C]DASB对30名极度肥胖（BMI范围在35至55kg/m²之间）和15名年龄和性别匹配的非肥胖志愿者（BMI范围在19至27kg/m²之间）进行了PET检查。5-HTT结合潜能（BPND）用作结果参数。
在组水平上，与非肥胖对照组相比，BMI最高的个体在各个皮质和皮质下区域的5-HTT BPND没有显著差异，而统计模型显示年龄、性别和抑郁程度对5-HTT BPND有轻微影响。
总体而言，肥胖个体中5-HTT可用性缺乏显著改变及其高变异性的发现，证明了对个体对外界和内部线索的行为反应进行研究的合理性，这可能进一步定义人类肥胖中不同的表型和亚组。
