Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.
Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.
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DOI：
10.1002/syn.21809
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发表时间：
2015-04
期刊：
影响因子：
2.3
通讯作者：
Small, Dana M.
中科院分区：
文献类型：
--
作者：
Cosgrove, Kelly P.;Veldhuizen, Maria G.;Sandiego, Christine M.;Morris, Evan D.;Small, Dana M.
临床和临床前研究的结果一致表明，肥胖增加和/或高脂肪饮食与背侧纹状体（DS）回路的改变有关。在人类中，体重指数（BMI）与背侧纹状体（DS）对美味食物消耗的反应之间存在可靠的反比关系。正电子发射断层扫描 (PET) 研究还表明，肥胖症中 DS 多巴胺 2/3 型受体 (D2R/D3R) 的可用性发生了改变；然而，该协会的方向尚不清楚。目前还不清楚多巴胺受体水平是否会导致较低的血氧水平依赖性（BOLD）反应，因为 PET 研究针对的是病态肥胖，而功能性磁共振成像（fMRI）研究很少包括 BMI 在此范围内的个体。因此，我们检查了 DS 对奶昔的 fMRI BOLD 反应是否与 BMI 范围从健康体重到中度肥胖的个体中使用 [11C]PHNO 和 PET 测量的 D2R/D3R 可用性相关。 29 名受试者参加了 fMRI 研究，12 名受试者参加了 [11C]PHNO PET 研究，其中 8 名受试者还完成了 fMRI 研究。正如预测的那样，DS BOLD 对奶昔的反应与 BMI 之间存在显着负相关。相反，BMI 与 D2R/D3R 可用性呈正相关。背侧纹状体 BOLD 反应与 D2R/D3R 可用性无关。在大量文献的背景下考虑，我们的结果表明 D2R/D3R 可用性与 BMI 之间存在非线性关系。此外，在肥胖中观察到的对可口食物消耗的 BOLD 反应改变与 D2R/D3R 受体可用性没有明显关系。
Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [11C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, twelve in the [11C]PHNO PET study, eight of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability.
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