Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats

Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats
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DOI:
10.1007/s00213-013-3013-0
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发表时间:
2013-07-01
期刊:
影响因子:
3.4
通讯作者:
Cifani, Carlo
Cifani, Carlo
中科院分区:
医学3区
文献类型:
--
作者:
Di Bonaventura, Maria Vittoria Micioni;Ubaldi, Massimo;Cifani, Carlo

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孤啡肽/孤啡肽FQ(N/OFQ)是促肾上腺皮质激素释放因子(corticotrophin-releasing factor,CRF)的功能性拮抗剂,是应激反应的主要介质。应激是导致高适口性食物暴饮暴食(BE)的关键因素,本文结合N/OFQ的抗应激特性,评价了其对BE的影响。在观察到食物限制增加了对食物限制的过度吞噬效应的敏感性之后,在食物限制循环之后,研究了NOP受体和N/OFQ的功能。在BE实验中,使用了四组大鼠:正常喂养而不应激或应激,大鼠暴露于限制/再喂养循环然后应激,或不应激。在其他实验中,两组大鼠被用来:暴露或不限制食物,只有限制和应激大鼠表现出对HPF(含巧克力奶油)的BE。侧脑室注射0.5 nmol/只N/OFQ可显著降低BE。N/OFQ 1 nmol/大鼠没有减少BE,但显着增加HPF摄入量后,食物限制。限食周期增加了动物对N/OFQ对HPF的吞噬作用的敏感性。食物限制后的原位杂交研究显示,终纹床核中ppN/OFQ mRNA表达降低,腹侧被盖区和腹内侧下丘脑中ppN/OFQ和NOP受体mRNA表达分别增加。这些发现表明,低剂量N/OFQ略微降低BE,而高剂量增加HPF摄入,因为在有热量限制的历史后,对它的吞噬作用的敏感性增加。
Nociceptin/orphanin FQ (N/OFQ) is a functional antagonist of corticotrophin-releasing factor, the main mediator of the stress response. Stress represents a key determinant of binge eating (BE) for highly palatable food (HPF).In relation to the antistress properties of N/OFQ, we evaluated its effect on BE. After the observation that episodes of food restriction increase the sensitivity to its hyperphagic effects, the function of NOP receptor and N/OFQ was investigated after cycles of food restrictions.In BE experiments, four groups were used: rats fed normally and not stressed or stressed, rats exposed to cycles of restriction/refeeding and then stressed, or not stressed. In the other experiments, two groups were used: rats exposed or not to food restriction.Only restricted and stressed rats exhibited BE for HPF (containing chocolate cream). Intracerebroventricular injections of N/OFQ of 0.5 nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but significantly increased HPF intake following food restrictions. Cycles of food restriction increased animals' sensitivity to the hyperphagic effect of N/OFQ for HPF. In situ hybridization studies following food restrictions showed decreased ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and increased expression of ppN/OFQ and NOP receptor mRNA in the ventral tegmental area and in the ventromedial hypothalamus, respectively.These findings indicate that N/OFQ slightly reduces BE at low doses, while higher doses increase HPF intake, due to increased sensitivity to its hyperphagic effect following a history of caloric restrictions.