Institute of Medical Psychology and Behavioral Neurobiology, fMEG Center, University of Tübingen, Tübingen, Germany.
PLoS One. 2013 Jun 14;8(6):e65893. doi: 10.1371/journal.pone.0065893. Print 2013.
Congenital leptin deficiency, caused by a very rare mutation in the gene encoding leptin, leads to severe obesity, hyperphagia and impaired satiety. The only systemic treatment is the substitution with metreleptin leading to weight reduction based on hormonal changes. Several studies have also shown alterations in brain function after metreleptin therapy. In a previous study, we were able to show changes in homeostatic (hypothalamus) and reward-related brain areas (striatum, orbitofrontal cortex (OFC), substantia nigra/ventral tegmental area, amygdala) 3 days and 6 months after therapy start in a leptin-deficient adolescent girl. To further access the time course of functional brain activation changes, we followed the patient for 2 years after initiation of the therapy. DESIGN, PATIENT: Functional magnetic resonance imaging during visual stimulation with food (high- and low-caloric) and non-food pictures was performed 1 and 2 years after therapy start in the previously described patient.
The comparison of 'food vs. non-food' pictures showed a stabilization of the long-term effects in the amygdala and in the OFC. Therefore, no significant differences were observed between 6 months compared to 12 and 24 months in these regions. Additionally, a reduction of the frontopolar cortex activity over the whole time span was observed. For the comparison of high- and low-caloric pictures, long-term effects in the hypothalamus showed an assimilating pattern for the response to the food categories whereas only acute effects after 3 months were observed in hedonic brain regions.
This follow-up study shows that the long lasting benefit of metreleptin therapy is also associated with activation changes in homeostatic, hedonic and frontal control regions in congenital leptin deficiency.
由编码瘦素的基因发生非常罕见的突变导致的先天性瘦素缺乏症，会引起严重肥胖、食欲过盛和饱腹感受损。唯一的全身治疗方法是用 metreleptin 替代，从而基于激素变化减轻体重。几项研究还表明 metreleptin 治疗后大脑功能发生改变。在之前的一项研究中，我们能够显示出在治疗开始后 3 天和 6 个月时，下丘脑的稳态（下丘脑）和与奖励相关的大脑区域（纹状体、眶额皮质（OFC）、黑质/腹侧被盖区、杏仁核）发生变化，在一名患有瘦素缺乏症的青少年女孩中。为了进一步了解功能大脑激活变化的时间过程，我们在开始治疗后 2 年对患者进行了随访。设计、患者：在治疗开始后 1 年和 2 年，对以前描述的患者进行了视觉刺激（高卡路里和低卡路里）和非食物图片的功能磁共振成像。
“食物与非食物”图片的比较显示，杏仁核和 OFC 的长期效应稳定。因此，与 6 个月相比，在这些区域中，12 个月和 24 个月之间没有观察到显著差异。此外，还观察到额极皮层活动的减少。对于高卡路里和低卡路里图片的比较，下丘脑的长期效应显示出对食物类别的反应同化模式，而在愉悦大脑区域仅观察到 3 个月后的急性效应。
这项随访研究表明，metreleptin 治疗的长期益处也与先天性瘦素缺乏症的稳态、愉悦和额叶控制区域的激活变化相关。
