Department of Internal Medicine I, University of Lübeck, Lübeck, Germany.
Department of Neurology, University of Lübeck, Lübeck, Germany; Institute of Psychology II, University of Lübeck, Lübeck, Germany.
Psychoneuroendocrinology. 2019 Jan;99:154-165. doi: 10.1016/j.psyneuen.2018.09.007. Epub 2018 Sep 8.
Short- and long-term treatment with glucocorticoids is widely used in clinical practice and frequently induces features of iatrogenic Cushing syndrome, such as abdominally centered weight gain. Despite decades of glucocorticoids usage, the mechanisms underlying these side effects are still only partly understood. One possibility is that glucocorticoids impact subcortical (hypothalamus, amygdala, insula) and cortical (orbitofrontal and cingulate cortex) brain regions involved in appetite regulation and reward processing. In the present study, we used functional magnetic resonance imaging (fMRI) to study the acute effects of a prednisolone infusion on reactivity of brain reward systems to food stimuli. Twenty healthy normal-weight men were tested in a randomized, double-blind, cross-over study. After an overnight fast and infusion of either 250 mg prednisolone or placebo (always administered between 8 and 9 A M), fMRI scans were taken while presenting food and object pictures in a Go/NoGo (GNG) task. At home, participants were asked to register what they had eaten. On the following morning they came back to the lab and had a supervised ad libitum breakfast at a standardized buffet. Food-Go in contrast to Object-Go pictures yielded increased blood oxygen level dependent (BOLD) activity in hippocampus, amygdala, orbitofrontal cortex, insula and anterior cingulate cortex. Prednisolone increased activation in the bilateral amygdala and right insula for approach-associated food pictures. The buffet test did not reveal significant differences in calorie consumption or preferences of different macronutrients. However, prednisolone-induced insula reactivity to Food-Go images was associated with greater caloric intake, both at home and in the standardized buffet. In sum, we observed a specific effect of prednisolone on the BOLD response of the amygdala and insula to approach-associated food stimuli. As these brain areas have previously been implicated in hedonic eating, the present pattern of results may reflect an increased anticipated reward value of food modulated by glucocorticoids. These effects might potentially drive increased food intake and weight gain under prolonged glucocorticoid treatment.
短期和长期使用糖皮质激素在临床实践中广泛应用，并经常引起医源性库欣综合征的特征，如以腹部为中心的体重增加。尽管使用糖皮质激素已有几十年的历史，但这些副作用的机制仍不完全清楚。一种可能性是糖皮质激素影响参与食欲调节和奖励处理的皮质下（下丘脑、杏仁核、岛叶）和皮质（眶额和扣带皮层）脑区。在本研究中，我们使用功能磁共振成像（fMRI）研究了泼尼松龙输注对食物刺激下大脑奖励系统反应性的急性影响。20 名健康的正常体重男性在一项随机、双盲、交叉研究中接受了测试。在禁食一夜和输注 250mg 泼尼松龙或安慰剂（始终在 8 点至 9 点之间给药）后，在进行食物和物体图片 Go/NoGo（GNG）任务时进行 fMRI 扫描。在家中，参与者被要求记录他们吃了什么。第二天早上，他们回到实验室，在标准化的自助餐上进行监督的自由进食早餐。与物体 Go 图片相比，食物 Go 图片引起了海马体、杏仁核、眶额皮层、岛叶和前扣带皮层的血氧水平依赖（BOLD）活性增加。泼尼松龙增加了双侧杏仁核和右侧岛叶对接近相关食物图片的激活。自助餐测试没有显示出卡路里摄入量或不同宏量营养素偏好的显著差异。然而，泼尼松龙诱导的对食物 Go 图像的岛叶反应与在家中和标准化自助餐中的更大热量摄入有关。总之，我们观察到泼尼松龙对与接近相关的食物刺激的杏仁核和岛叶的 BOLD 反应有特定的影响。由于这些脑区先前与享乐性进食有关，因此目前的结果模式可能反映了糖皮质激素调节的食物预期奖励价值的增加。这些影响可能会导致在长期糖皮质激素治疗下增加食物摄入和体重增加。
