van Galen Katy A, Booij Jan, Schrantee Anouk, Adriaanse Sofie M, Unmehopa Unga A, Fliers Eric, Schwartz Gary J, DiLeone Ralph J, Ter Horst Kasper W, la Fleur Susanne E, Serlie Mireille J
Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.
Metabolism. 2021 Oct;123:154839. doi: 10.1016/j.metabol.2021.154839. Epub 2021 Jul 29.
Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity.
In this randomized controlled cross-over trial, we assessed the effects of 12 vs 24 h of fasting on SERT and DAT availability in the hypothalamus/thalamus and striatum, respectively, using SPECT imaging in 10 lean men and 10 men with obesity.
As compared with the 12-h fast, a 24-h fast increased hypothalamic SERT availability in lean men, but not in men with obesity. We observed high inter-individual variation in the effects of fasting on thalamic SERT and striatal DAT, with no differences between lean men and those with obesity. In all subjects, fasting-induced increases in circulating free fatty acid (FFA) concentrations were associated with an increase in hypothalamic SERT availability and a decrease in striatal DAT availability. Multiple regression analysis showed that changes in plasma insulin and FFAs together accounted for 44% of the observed variation in striatal DAT availability.
Lean men respond to prolonged fasting by increasing hypothalamic SERT availability, whereas this response is absent in men with obesity. Inter-individual differences in the adaptations of the cerebral serotonergic and dopaminergic systems to fasting may, in part, be explained by changes in peripheral metabolic signals of fasting, including FFAs and insulin.
大脑中的血清素能和多巴胺能系统对于食物摄入和全身能量代谢的稳态及奖赏相关调节至关重要。目前尚不清楚禁食如何影响这些系统，以及肥胖人群中这些影响是否会发生改变。因此，我们旨在评估禁食对瘦素正常者和肥胖者下丘脑/丘脑血清素转运体（SERT）及纹状体多巴胺转运体（DAT）可用性的影响。
在这项随机对照交叉试验中，我们对10名瘦素正常男性和10名肥胖男性进行单光子发射计算机断层扫描（SPECT）成像，分别评估禁食12小时和24小时对下丘脑/丘脑及纹状体中SERT和DAT可用性的影响。
与禁食12小时相比，禁食24小时使瘦素正常男性下丘脑SERT可用性增加，但肥胖男性未出现此变化。我们观察到禁食对丘脑SERT和纹状体DAT的影响存在较大个体差异，瘦素正常男性与肥胖男性之间无差异。在所有受试者中，禁食诱导的循环游离脂肪酸（FFA）浓度升高与下丘脑SERT可用性增加及纹状体DAT可用性降低相关。多元回归分析表明，血浆胰岛素和FFA的变化共同解释了纹状体DAT可用性观察到的44%的变异。
瘦素正常男性通过增加下丘脑SERT可用性对延长禁食做出反应，而肥胖男性则无此反应。大脑血清素能和多巴胺能系统对禁食适应的个体差异，部分可能由禁食外周代谢信号的变化所解释，包括FFA和胰岛素。
