Darcey Valerie L, Guo Juen, Chi Meible, Chung Stephanie T, Courville Amber B, Gallagher Isabelle, Herscovitch Peter, Howard Rebecca, LaNoire Melissa, Milley Lauren, Schick Alex, Stagliano Michael, Turner Sara, Urbanski Nicholas, Yang Shanna, Yim Eunha, Zhai Nan, Zhou Megan S, Hall Kevin D
Integrative Physiology Section, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, USA.
medRxiv. 2023 Sep 28:2023.09.27.23296169. doi: 10.1101/2023.09.27.23296169.
The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [F]fallypride and [C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [C]raclopride (r= -0.51; p<0.0001) but not [F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [F]fallypride has greater binding affinity to dopamine type-2 receptors than [C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.
20多年来,人们反复研究了人体大脑中肥胖与多巴胺2型受体结合潜力(D2BP)之间的关系,但结果差异很大,这可能是由于方法不同和研究人群不同所致。我们进行了一项对照住院喂养研究,对54名体重指数(BMI)范围较广(20-44kg/m²)的年轻成年人,以伪随机顺序使用[F]氟哌利多和[C]雷氯必利通过正电子发射断层扫描测量纹状体中的D2BP。使用两种示踪剂进行的受试者内D2BP测量呈中度相关(r=0.47,p<0.001)。通过[C]雷氯必利测量,D2BP与BMI呈负相关(r=-0.51;p<0.0001),但与[F]氟哌利多不相关(r=-0.01;p=0.92),并且这些相关系数彼此显著不同(p<0.001)。鉴于[F]氟哌利多对多巴胺2型受体的结合亲和力大于[C]雷氯必利,而[C]雷氯必利更容易被内源性多巴胺取代,我们的结果表明肥胖与纹状体多巴胺能张力增加呈正相关。