Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.
Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada.
Transl Psychiatry. 2021 May 1;11(1):259. doi: 10.1038/s41398-021-01370-2.
Obesity is a growing burden to health and the economy worldwide. Obesity is associated with central µ-opioid receptor (MOR) downregulation and disruption of the interaction between MOR and dopamine D receptor (DR) system in the ventral striatum. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying 20 healthy non-obese and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and DR availability were measured using positron emission tomography (PET) with [C]carfentanil and [C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed on obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. In the control subjects, MOR and DR availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but the unaltered association in dorsal caudate (r = .43). The association between MOR and DR availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss. Bariatric surgery and concomitant weight loss recover the interaction between MOR and DR in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioral interventions for treating obesity.
肥胖是全球范围内日益严重的健康和经济负担。肥胖与中脑 μ-阿片受体（MOR）下调以及腹侧纹状体中 MOR 与多巴胺 D 受体（DR）系统相互作用的破坏有关。体重减轻会恢复 MOR 功能，但尚不清楚它是否也能恢复异常的阿片类-多巴胺相互作用。在这里，我们通过研究 20 名健康的非肥胖者和 25 名病态肥胖者（平均 BMI 为 41）来解决这个问题，这些人有资格接受减肥手术。使用正电子发射断层扫描（PET）分别用 [C]carfentanil 和 [C]raclopride 测量大脑 MOR 和 DR 的可用性。根据标准临床治疗，对肥胖患者进行 Roux-en-Y 胃旁路或袖状胃切除术。21 名肥胖患者在减肥手术后 6 个月参加了术后 PET 扫描。在对照组中，腹侧纹状体（r=.62）和背侧尾状核（r=.61）中的 MOR 和 DR 可用性相关。术前，肥胖患者腹侧纹状体中的关联被破坏（r=.12），但背侧尾状核中的关联未改变（r=.43）。减肥手术后，肥胖患者腹侧纹状体中 MOR 和 DR 可用性之间的关联得到恢复（r=.62）。减肥手术和随之而来的体重减轻恢复了肥胖患者腹侧纹状体中 MOR 和 DR 之间的相互作用。因此，腹侧纹状体中功能失调的阿片类-多巴胺相互作用可能与肥胖表型有关，并可能介导过多的能量摄取。纹状体阿片类-多巴胺相互作用为治疗肥胖的药物和行为干预提供了一个可行的靶点。
