Calorie seeking, but not hedonic response, contributes to hyperphagia in a mouse model for Prader-Willi syndrome.
Calorie seeking, but not hedonic response, contributes to hyperphagia in a mouse model for Prader-Willi syndrome.
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DOI：
10.1111/ejn.12972
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Isles AR
中科院分区：
文献类型：
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作者：
Davies JR;Humby T;Dwyer DM;Garfield AS;Furby H;Wilkinson LS;Wells T;Isles AR
Prader-Willi氏综合征(PWS)是一种神经发育障碍，由人类染色体15q11-q13上父性表达的印记基因缺失或失活引起，其最常见的特征是吞噬功能亢进。这被认为是由于对食物的生理驱动力和食物的有益特性的异常造成的。尽管存在一些PWS的小鼠模型，但决定不适应进食的潜在变量仍然未知。这里，描述了缺失同音PWS间隔的印记中心(IC)的小鼠模型(PWS ICdel小鼠)的摄食行为。研究表明，PWS ICdel小鼠在隔夜禁食和加蔗糖后都表现出高生长激素血症和食物消耗量增加。然而，PWS ICdel小鼠的过度吞噬并没有伴随着对可口食物(蔗糖或糖精)的享乐特性的任何反应性变化，这是通过舔舔簇大小来衡量的。然而，在舔食试验中，PWS ICdel小鼠对非热量糖精的总摄入量显著减少。结合持续强化计划的汇聚发现，这些数据表明PWS ICdel小鼠对食物的热值表现出显著的高度敏感性。总体而言，这些数据表明，食物的有益特性对PWS ICdel小鼠过度吞噬的任何影响主要是由卡路里含量驱动的，不太可能涉及享乐过程。这对于理解PWS摄食表型的神经系统以及印记基因在更普遍的异常摄食行为中的作用具有重要意义。
Prader–Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11‐q13, the most recognised feature of which is hyperphagia. This is thought to arise as a consequence of abnormalities in both the physiological drive for food and the rewarding properties of food. Although a number of mouse models for PWS exist, the underlying variables dictating maladaptive feeding remain unknown. Here, feeding behaviour in a mouse model in which the imprinting centre (IC) of the syntenic PWS interval has been deleted (PWS ICdel mice) is characterised. It is demonstrated that PWS ICdel mice show hyperghrelinaemia and increased consumption of food both following overnight fasting and when made more palatable with sucrose. However, hyperphagia in PWS ICdel mice was not accompanied by any changes in reactivity to the hedonic properties of palatable food (sucrose or saccharin), as measured by lick‐cluster size. Nevertheless, overall consumption by PWS ICdel mice for non‐caloric saccharin in the licking test was significantly reduced. Combined with converging findings from a continuous reinforcement schedule, these data indicate that PWS ICdel mice show a marked heightened sensitivity to the calorific value of food. Overall, these data indicate that any impact of the rewarding properties of food on the hyperphagia seen in PWS ICdel mice is driven primarily by calorie content and is unlikely to involve hedonic processes. This has important implications for understanding the neural systems underlying the feeding phenotype of PWS and the contribution of imprinted genes to abnormal feeding behaviour more generally.