Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Obes Surg. 2010 Mar;20(3):369-74. doi: 10.1007/s11695-009-0015-4. Epub 2009 Oct 29.
While bariatric surgery has proved highly successful at producing sustained weight loss, variability in treatment response persists. A better understanding of the pathophysiology of appetite and obesity may improve patient selection and management. Research into feeding behavior and satiety has focused on the role of dopamine in reward-based behaviors. Specifically, positron-emission computed tomography (PET) has demonstrated reduced brain dopamine receptor availability in obese subjects compared to controls. This may be due to a primary deficiency in dopamine receptors or to secondary dopamine receptor downregulation. We performed a preliminary study to investigate dopamine D2 receptor activity in obese subjects before and after laparoscopic Roux-en Y gastric bypass (LGBP).
Five female subjects, ages 20 to 38 years old with a mean body mass index of 45, underwent PET with [C-11] raclopride injection. Five regions of interest were studied: ventral striatum, anterior and posterior putamen, and anterior and posterior caudate nucleus. Repeat PET was performed at 6 weeks following LGBP. D2 receptor binding was compared within subjects pre- and post-surgery. Baseline D2 binding was also compared to historical nonobese controls.
D2 receptor availability increased 6 weeks after gastric bypass surgery. The increase in receptor availability appeared roughly proportional to the amount of weight lost. No significant difference in D2 binding was seen between the obese subjects and historical nonobese controls.
Brain available dopamine D2 binding appears to increase following GBP. This preliminary finding needs to be replicated in a larger population but suggests that diminished D2 binding in the obese may be due to D2 receptor downregulation. Changes in available dopamine receptor binding may play an important role in centrally mediated appetite suppression and resultant weight loss after LGBP.
减重手术在实现持续减重方面已被证明非常成功,但治疗反应的可变性仍然存在。更好地了解食欲和肥胖的病理生理学可能会改善患者的选择和管理。对摄食行为和饱腹感的研究集中在多巴胺在基于奖励的行为中的作用。具体来说,正电子发射计算机断层扫描(PET)已经证明,与对照组相比,肥胖受试者的大脑多巴胺受体可用性降低。这可能是由于多巴胺受体的原发性缺乏,也可能是由于多巴胺受体的继发性下调。我们进行了一项初步研究,以调查肥胖患者在腹腔镜 Roux-en Y 胃旁路术(LGBP)前后的多巴胺 D2 受体活性。
5 名年龄在 20 至 38 岁之间、平均体重指数为 45 的女性受试者接受了 [C-11] raclopride 注射的 PET。研究了 5 个感兴趣的区域:腹侧纹状体、前和后纹状体、前和后尾状核。在 LGBP 后 6 周进行重复 PET。在手术前后对受试者内的 D2 受体结合进行比较。还将基线 D2 结合与历史上的非肥胖对照组进行了比较。
胃旁路手术后 6 周,D2 受体的可用性增加。受体可用性的增加似乎与体重减轻的量大致成正比。肥胖受试者与历史非肥胖对照组之间的 D2 结合无显著差异。
GBP 后大脑中可用的多巴胺 D2 结合似乎增加。这一初步发现需要在更大的人群中得到复制,但表明肥胖者中 D2 结合的减少可能是由于 D2 受体下调所致。可用多巴胺受体结合的变化可能在 LGBP 后中枢介导的食欲抑制和体重减轻中发挥重要作用。