Wei Nai-Li, Quan Zi-Fang, Zhao Tong, Yu Xu-Dong, Xie Qiang, Zeng Jun, Ma Fu-Kai, Wang Fan, Tang Qi-Sheng, Wu Heng, Zhu Jian-Hong
Fudan University Huashan Hospital, Department of Neurosurgery, State Key Laboratory for Medical neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University, Shanghai, 20040, People's Republic of China.
Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou Gansu China, 730030, People's Republic of China.
Neuropsychiatr Dis Treat. 2019 May 8;15:1211-1229. doi: 10.2147/NDT.S204818. eCollection 2019.
Stress-related obesity might be related to the suppression of the hypothalamic-pituitary- adrenocortical axis and dysregulation of the metabolic system. Chronic stress also induces the dysregulation of the reward system and increases the risk of food addiction, according to recent clinical findings. However, few studies have tested the effect of chronic stress on food addiction in animal models. The objective of this study was to identify whether chronic stress promotes food addiction or not and explore the possible mechanisms. We applied adaily 2 hrsflashing LED irradiation stress to mice fed chow or palatable food to mimic the effect of chronic stress on feeding. After 1 month of chronic stress exposure, we tested their binge eating behaviors, cravings for palatable food, responses for palatable food, and compulsive eating behaviors to evaluate the effect of chronic stress on food addiction-like behaviors. We detected changes in the levels of various genes and proteins in the nucleus accumbens (NAc), ventral tegmental area (VTA) and lateral hypothalamus using qPCR and immunofluorescence staining, respectively. Behaviors results indicated chronic stress obviously increased food addiction score (FAS) in the palatable food feeding mice. Moreover, the FAS had astrong relationship with the extent of the increase in body weight. Chronic stress increased the expression of corticotropin-releasing factor receptor 1(CRFR1) was increased in the NAc shell and core but decreased in the VTA of the mice fed with palatable food. Chronic stress also increased expression of both dopamine receptor 2 (DR2) and mu-opioid receptor (MOR) in the NAc. Chronic stress aggravates the FAS and contributed to the development of stress-related obesity. Chronic stress drives the dysregulation of the CRF signaling pathway in the reward system and increases the expression of DR2 and MOR in the nucleus accumbens.
应激相关肥胖可能与下丘脑 - 垂体 - 肾上腺皮质轴的抑制及代谢系统失调有关。根据最近的临床研究结果，慢性应激还会导致奖赏系统失调并增加食物成瘾的风险。然而，很少有研究在动物模型中测试慢性应激对食物成瘾的影响。本研究的目的是确定慢性应激是否会促进食物成瘾，并探索其可能的机制。我们对喂食普通食物或美味食物的小鼠施加每天2小时的LED闪烁光照应激，以模拟慢性应激对进食的影响。在慢性应激暴露1个月后，我们测试了它们的暴饮暴食行为、对美味食物的渴望、对美味食物的反应以及强迫性进食行为，以评估慢性应激对食物成瘾样行为的影响。我们分别使用qPCR和免疫荧光染色检测了伏隔核（NAc）、腹侧被盖区（VTA）和下丘脑外侧区各种基因和蛋白质水平的变化。行为结果表明，慢性应激明显增加了喂食美味食物小鼠的食物成瘾评分（FAS）。此外，FAS与体重增加程度密切相关。慢性应激使喂食美味食物小鼠的NAc壳和核心中促肾上腺皮质激素释放因子受体1（CRFR1）的表达增加，但VTA中的表达降低。慢性应激还增加了NAc中多巴胺受体2（DR2）和μ-阿片受体（MOR）的表达。慢性应激加剧了FAS，并导致应激相关肥胖的发展。慢性应激导致奖赏系统中CRF信号通路失调，并增加伏隔核中DR2和MOR的表达。
