Schlögl Haiko, Janssen Lieneke, Fasshauer Mathias, Miehle Konstanze, Villringer Arno, Stumvoll Michael, Mueller Karsten
Department of Medicine, University Hospital Leipzig, 04103 Leipzig, Germany.
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, 04103 Leipzig, Germany.
J Endocr Soc. 2023 Apr 20;7(6):bvad052. doi: 10.1210/jendso/bvad052. eCollection 2023 May 5.
Behaviorally, the most pronounced effects of leptin substitution in leptin deficiency are the hunger-decreasing and postprandial satiety-prolonging effects of the adipokine. Previously, with functional magnetic resonance imaging (MRI), we and others showed that eating behavior-controlling effects are at least in part conveyed by the reward system. However, to date, it is unclear if leptin only modulates eating behavior specific brain reward action or if it also alters the reward function of the brain unrelated to eating behavior.
We investigated with functional MRI the effects of metreleptin on the reward system in a reward task unrelated to eating behavior, the monetary incentive delay task.
Measurements in 4 patients with the very rare disease of lipodystrophy (LD), resulting in leptin deficiency, and 3 untreated healthy control persons were performed at 4 different time points: before start and over 12 weeks of metreleptin treatment. Inside the MRI scanner, participants performed the monetary incentive delay task and brain activity during the reward receipt phase of the trial was analyzed.
We found a reward-related brain activity decrease in our 4 patients with LD over the 12 weeks of metreleptin treatment in the subgenual region, a brain area associated with the reward network, which was not observed in our 3 untreated healthy control persons.
These results suggest that leptin replacement in LD induces changes of brain activity during reward reception processing completely unrelated to eating behavior or food stimuli. This could suggest eating behavior-unrelated functions of leptin in the human reward system.
The trial is registered as trial No. 147/10-ek at the ethics committee of the University of Leipzig and at the State Directorate of Saxony (Landesdirektion Sachsen).
从行为学角度来看，在瘦素缺乏症中进行瘦素替代治疗最显著的效果是该脂肪因子具有减少饥饿感和延长餐后饱腹感的作用。此前，我们和其他研究人员通过功能磁共振成像（MRI）表明，控制饮食行为的作用至少部分是由奖赏系统传递的。然而，迄今为止，尚不清楚瘦素是否仅调节与饮食行为相关的特定脑奖赏作用，还是也会改变与饮食行为无关的脑奖赏功能。
我们通过功能磁共振成像研究了美曲普明在与饮食行为无关的奖赏任务——金钱激励延迟任务中对奖赏系统的影响。
对4例患有极为罕见的脂肪营养不良症（LD）导致瘦素缺乏的患者以及3名未经治疗的健康对照者在4个不同时间点进行测量：在美曲普明治疗开始前和治疗12周期间。在MRI扫描仪内，参与者执行金钱激励延迟任务，并分析试验奖赏接收阶段的脑活动。
我们发现，在美曲普明治疗的12周内，我们的4例LD患者在膝下区域（一个与奖赏网络相关的脑区）出现了与奖赏相关的脑活动减少，而在3名未经治疗的健康对照者中未观察到这种情况。
这些结果表明，在LD患者中进行瘦素替代治疗会在奖赏接收过程中诱发与饮食行为或食物刺激完全无关的脑活动变化。这可能提示瘦素在人类奖赏系统中具有与饮食行为无关的功能。
该试验已在莱比锡大学伦理委员会和萨克森州政府（Landesdirektion Sachsen）注册，试验编号为147/10 - ek。
