Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat
Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat
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DOI：
10.1007/s00394-017-1434-y
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发表时间：
2018-06-01
影响因子：
5
通讯作者：
Gaetani, Silvana
中科院分区：
文献类型：
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作者：
Coccurello, Roberto;Romano, Adele;Gaetani, Silvana
长期暴露于压力可能是代谢和饮食失调的危险因素，主要是由于过度消费容易获得的能量密集的美味食物，尽管所涉及的机制仍不清楚。在这项研究中，我们使用了行为学导向的慢性压力造成的慢性心理社会失败（CPD）的小鼠模型，调查的影响，不受限制地获得一个可口的高脂肪饮食（HFD）的食物摄入量，体重，能量稳态，和不同的脑神经肽的表达。我们的目的是阐明的机制，负责体重和身体成分的变化，由于慢性社会stress.Methods在我们的模型下属（失败），小鼠（CPD）同居在不断的感官接触占主导地位，被迫每天进行互动，并提供随意访问HFD或控制饮食（CD）。对照小鼠（与CPD小鼠相同品系）成对饲养，并在其饲养笼（UN）中不受应激。在所有这些小鼠中，我们评估了体重，不同的脂肪库，能量代谢，热量摄入，和neuropeptide expression.Results CPD小鼠增加了摄入的HFD和降低体重的存在下，增强脂质氧化。CPD小鼠的静息能量消耗和肩胛间棕色脂肪组织（iBAT）增加，而附睾脂肪组织仅在HFD喂养的无应激小鼠中增加。下丘脑弓状核中的Propiomelanocortin mRNA水平仅在HFD喂养的未应激小鼠中增加。室旁核中催产素mRNA水平和弓状核中神经肽Y mRNA水平仅在CD喂养的CPD小鼠中增加。在弓形体中，HFD喂养的UN小鼠和CD喂养的CPD小鼠的CART增加，而HFD摄入抑制了失败动物的CART增加。在基底外侧杏仁核中，CART表达增加，只有在CPD动物HFD.Conclusions出现解耦的摄入HFD的能量稳态，导致更高的HFD摄入量，更大的iBAT积累，增加能量消耗和脂质氧化，降低体重。总体而言，本研究证实了这样的概念，即应激反应的慢性激活可能与代谢紊乱、能量稳态改变以及食欲和食欲信号的变化有关。这些变化可能与更好地了解应激诱导的肥胖和饮食失调的病因有关，并可能代表了在该领域开发新疗法的有效治疗方法。
Purpose Chronic exposure to stress may represent a risk factor for developing metabolic and eating disorders, mostly driven by the overconsumption of easily accessible energy-dense palatable food, although the mechanisms involved remain still unclear. In this study, we used an ethologically oriented murine model of chronic stress caused by chronic psychosocial defeat (CPD) to investigate the effects of unrestricted access to a palatable high fat diet (HFD) on food intake, body weight, energy homeostasis, and expression of different brain neuropeptides. Our aim was to shed light on the mechanisms responsible for body weight and body composition changes due to chronic social stress.Methods In our model of subordinate (defeated), mice (CPD) cohabitated in constant sensory contact with dominants, being forced to interact on daily basis, and were offered ad libitum access either to an HFD or to a control diet (CD). Control mice (of the same strain as CPD mice) were housed in pairs and left unstressed in their home cage (UN). In all these mice, we evaluated body weight, different adipose depots, energy metabolism, caloric intake, and neuropeptide expression.Results CPD mice increased the intake of HFD and reduced body weight in the presence of enhanced lipid oxidation. Resting energy expenditure and interscapular brown adipose tissue (iBAT) were increased in CPD mice, whereas epididymal adipose tissue increased only in HFD-fed unstressed mice. Propiomelanocortin mRNA levels in hypothalamic arcuate nucleus increased only in HFD-fed unstressed mice. Oxytocin mRNA levels in the paraventricular nucleus and neuropeptide Y mRNA levels within the arcuate were increased only in CD-fed CPD mice. In the arcuate, CART was increased in HFD-fed UN mice and in CD-fed CPD mice, while HFD intake suppressed CART increase in defeated animals. In the basolateral amygdala, CART expression was increased only in CPD animals on HFD.Conclusions CPD appears to uncouple the intake of HFD from energy homeostasis causing higher HFD intake, larger iBAT accumulation, increased energy expenditure and lipid oxidation, and lower body weight. Overall, the present study confirms the notion that the chronic activation of the stress response can be associated with metabolic disorders, altered energy homeostasis, and changes of orexigenic and anorexigenic signaling. These changes might be relevant to better understand the etiology of stress-induced obesity and eating disorders and might represent a valid therapeutic approach for the development of new therapies in this field.