Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, London, UK.
Psychiatric Imaging Group, Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London, UK.
J Psychopharmacol. 2021 May;35(5):606-610. doi: 10.1177/0269881120965912. Epub 2021 Jan 6.
A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers.
Seven volunteers each completed a baseline [C]carfentanil PET scan followed by an administration of sodium acetate before a second [C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [C] carfentanil values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [C]carfentanil following acetate administration.
Following sodium acetate administration, 2.5-6.5% reductions in [C]carfentanil regional were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus.
We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.
最近的一项研究表明，醋酸盐给药会导致下丘脑中前阿黑皮素原（POMC）mRNA 的转录增加四倍。POMC 被切割成肽，包括β-内啡肽，一种内源性阿片（EO）激动剂，它优先与μ-阿片受体（MOR）结合。我们假设醋酸盐挑战会增加人脑中的 EO 水平。我们之前已经证明，使用正电子发射断层扫描（PET）和选择性 MOR 放射性配体 [C]卡芬太尼可以检测到人脑 EO 释放的增加。我们使用这种方法来评估急性醋酸盐挑战对健康人类志愿者大脑中 EO 水平的影响。
7 名志愿者每人都完成了基线 [C]carfentanil PET 扫描，然后在第二次 [C]carfentanil PET 扫描前给予醋酸钠。动态 PET 数据在 90 分钟内采集，并进行衰减、散射和受试者运动校正。然后使用简化参考组织模型（以枕叶灰质为参考区域）计算区域 [C]carfentanil 值。通过在醋酸盐给药后评估 [C]carfentanil 的变化来评估 EO 浓度的变化。
给予醋酸钠后，[C]carfentanil 区域的减少率为 2.5-6.5%，小脑、颞叶、眶额皮质、纹状体和丘脑达到统计学意义。
我们已经证明，急性醋酸盐挑战有可能增加人脑中的 EO 释放，为醋酸盐对人类食欲的中枢作用提供了一种合理的机制。
