Lapo Pais Marta, Crisóstomo Joana, Abrunhosa Antero, Castelo-Branco Miguel
Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.
Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal.
Commun Med (Lond). 2025 Aug 28;5(1):375. doi: 10.1038/s43856-025-01079-z.
Central mechanisms may play a role in the success of bariatric surgery (BS), the treatment of choice for refractory obesity. We hypothesize that central dopaminergic receptor function in striatal brain regions is a pivotal mechanism in the success of BS.
We conducted a cross-sectional study to investigate central dopamine type 2 and 3 receptors (D2/3 R) within striatal brain regions in successful weight loss (WL) through BS. Positron Emission Tomography was used to map nondisplaceable binding potential (BP) of D2/3 R in 48 women: 19 successful responders to BS, 12 with obesity (OB), and 17 normal-weight controls. Parametric maps were compared between-groups in regions of interest and at voxel-level. We also investigated brain blood oxygenation level-dependent (BOLD) responses to food content using functional Magnetic Resonance Imaging (fMRI) and how key variables correlate with D2/3 R binding.
We find mean D2/3 R BP significant differences between OB and controls in the ventral striatum (p = 0.042) and at voxel-level across striatum between OB and the other groups (p < 0.05). Food content (Food > Non-food, p = 0.05) reveals significantly higher neural activation in striatum also for OB compared to the other groups. Moreover, D2/3 R BP values correlate with dysfunctional self-report measures of eating behaviors, incentive salience to food cue and high-calorie food preferences in obesity. Notably, BOLD responses (Food > Baseline) in striatum correlate positively with D2/3 R binding in ventral striatum.
Striatal dopaminergic dysfunction in obesity may enhance salience to food cues, driving cravings and compulsive eating. BS may reverse the striatal molecular and functional disruptions found in obesity.
中枢机制可能在减肥手术（BS）的成功中发挥作用，减肥手术是治疗难治性肥胖的首选方法。我们假设纹状体脑区的中枢多巴胺能受体功能是减肥手术成功的关键机制。
我们进行了一项横断面研究，以调查通过减肥手术成功减重（WL）的患者纹状体脑区内的中枢多巴胺2型和3型受体（D2/3R）。使用正电子发射断层扫描来绘制48名女性中D2/3R的不可置换结合潜能（BP）：19名减肥手术成功应答者、12名肥胖者（OB）和17名正常体重对照者。在感兴趣区域和体素水平上比较各组之间的参数图。我们还使用功能磁共振成像（fMRI）研究了大脑血氧水平依赖（BOLD）对食物内容的反应，以及关键变量与D2/3R结合的相关性。
我们发现腹侧纹状体中OB组与对照组之间的平均D2/3R BP存在显著差异（p = 0.042），并且在纹状体的体素水平上，OB组与其他组之间也存在显著差异（p < 0.05）。食物内容（食物>非食物，p = 0.05）显示，与其他组相比，OB组纹状体中的神经激活也显著更高。此外，D2/3R BP值与肥胖患者饮食行为的功能失调自我报告测量、对食物线索的动机显著性和高热量食物偏好相关。值得注意的是，纹状体中的BOLD反应（食物>基线）与腹侧纹状体中的D2/3R结合呈正相关。
肥胖中的纹状体多巴胺能功能障碍可能会增强对食物线索的显著性，引发渴望和强迫性进食。减肥手术可能会逆转肥胖中发现的纹状体分子和功能破坏。
