Schweickert de Palma Eva, Günnewig Tilman, Rullmann Michael, Luthardt Julia, Hankir Mohammed K, Meyer Philipp M, Becker Georg-Alexander, Patt Marianne, Martin Sarah, Hilbert Anja, Blüher Matthias, Sabri Osama, Hesse Swen
Department of Nuclear Medicine, University of Leipzig, 04013 Leipzig, Germany.
Integrated Research and Treatment Center Adiposity Diseases, Leipzig University Medical Centre, 04103 Leipzig, Germany.
Brain Sci. 2022 Dec 1;12(12):1648. doi: 10.3390/brainsci12121648.
Obesity is thought to arise, in part, from deficits in the inhibitory control over appetitive behavior. Such motivational processes are regulated by neuromodulators, specifically acetylcholine (ACh), via α4β2* nicotinic ACh receptors (nAChR). These nAChR are highly enriched in the thalamus and contribute to the thalamic gating of cortico-striatal signaling, but also act on the mesoaccumbal reward system. The changes in α4β2* nAChR availability, however, have not been demonstrated in human obesity thus far. The aim of our study was, thus, to investigate whether there is altered brain α4β2* nAChR availability in individuals with obesity compared to normal-weight healthy controls.
We studied 15 non-smoking individuals with obesity (body mass index, BMI: 37.8 ± 3.1 kg/m; age: 39 ± 14 years, 9 females) and 16 normal-weight controls (non-smokers, BMI: 21.9 ± 1.7 kg/m; age: 28 ± 7 years, 13 females) by using PET and the α4β2* nAChR selective (-)-[F]flubatine, which was applied within a bolus-infusion protocol (294 ± 16 MBq). Volume-of-interest (VOI) analysis was performed in order to calculate the regional total distribution volume (V).
No overall significant difference in V between the individuals with obesity and the normal-weight volunteers was found, while the V in the nucleus basalis of Meynert tended to be lower in the individuals with obesity (10.1 ± 2.1 versus 11.9 ± 2.2; = 0.10), and the V in the thalamus showed a tendency towards higher values in the individuals with obesity (26.5 ± 2.5 versus 25.9 ± 4.2; = 0.09).
While these first data do not show greater brain α4β2* nAChR availability in human obesity overall, the findings of potentially aberrant α4β2* nAChR availability in the key brain regions that regulate feeding behavior merit further exploration.
肥胖被认为部分源于对食欲行为抑制控制的缺陷。这种动机过程由神经调质，特别是乙酰胆碱（ACh），通过α4β2烟碱型乙酰胆碱受体（nAChR）进行调节。这些nAChR在丘脑中高度富集，有助于皮质 - 纹状体信号的丘脑门控，也作用于中脑伏隔核奖赏系统。然而，迄今为止，α4β2 nAChR可用性的变化在人类肥胖中尚未得到证实。因此，我们研究的目的是调查与正常体重的健康对照相比，肥胖个体的脑α4β2* nAChR可用性是否发生改变。
我们使用PET和α4β2* nAChR选择性（-）-[F]氟巴汀研究了15名肥胖的非吸烟个体（体重指数，BMI：37.8±3.1 kg/m²；年龄：39±14岁，9名女性）和16名正常体重对照（非吸烟者，BMI：21.9±1.7 kg/m²；年龄：28±7岁，13名女性），该药物采用团注 - 输注方案（294±16 MBq）给药。进行感兴趣区（VOI）分析以计算区域总分布容积（V）。
未发现肥胖个体与正常体重志愿者之间的V存在总体显著差异，而肥胖个体中Meynert基底核的V倾向于较低（10.1±2.1对11.9±2.2；P = 0.10），丘脑中的V在肥胖个体中显示出较高值的趋势（26.5±2.5对25.9±4.2；P = 0.09）。
虽然这些初步数据并未显示人类肥胖总体上脑α4β2* nAChR可用性更高，但在调节进食行为的关键脑区中α4β2* nAChR可用性潜在异常的发现值得进一步探索。
