High ambient temperature reverses hypothalamic MC4 receptor overexpression in an animal model of anorexia nervosa
High ambient temperature reverses hypothalamic MC4 receptor overexpression in an animal model of anorexia nervosa
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DOI：
10.1016/j.psyneuen.2008.10.003
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发表时间：
2009-04-01
影响因子：
3.7
通讯作者：
Echevarria, E.
中科院分区：
文献类型：
--
作者：
Gutierrez, E.;Churruca, I.;Echevarria, E.
研究了黑皮质素系统在热敷对患有基于活动的厌食症（ABA）（神经性厌食症（AN）的类似模型）的大鼠的有益影响中的潜在参与。一旦 ABA 大鼠体重减轻 20%，一半的动物就会暴露在 32 摄氏度的高环境温度 (HAT) 下，而其余的则维持在 21 摄氏度。与 ABA 动物交配的对照久坐大鼠接受相同的治疗。与对照组相比，ABA 大鼠（21 摄氏度）黑皮质素 4 (MC4) 受体和刺鼠基因相关肽 (AgRP) 表达增加，阿片黑皮质素原 (POMC) mRNA 水平降低（实时 PCR）。与 21 摄氏度的 ABA 大鼠相比，加热增加了 ABA 大鼠的体重增加和食物摄入量，并降低了跑步速度。然而，在暴露于热源的久坐大鼠中，没有观察到体重和食物摄入量的变化。此外，热敷降低了ABA大鼠中MC4受体、AgRP和POMC的表达，但在对照大鼠中没有观察到变化。这些结果表明，下丘脑 MC4 受体过度表达可能是由于 ABA 大鼠特征性多动、体重抛掷和自我饥饿而发生的，并表明下丘脑黑皮质素神经回路参与了 AN 患者表现出的行为变化。 AgRP 和 POMC 表达的变化可能代表对平衡能量平衡的适应性反应。此外，HAT 逆转 ABA 大鼠下丘脑 MC4 受体过度表达的事实表明，大脑黑皮质素系统参与了报道的热敷对 AN 的有益作用。 MC4 受体拮抗剂和热敷相结合可以改善 AN 的临床治疗。 (C) 2008 Elsevier Ltd. 保留所有权利。
The potential involvement of the melanocortin system in the beneficial effects of heat application in rats submitted to activity-based anorexia (ABA), an analogous model of anorexia nervosa (AN), was studied. Once ABA rats had lost 20% of body weight, half of the animals were exposed to a high ambient temperature (HAT) of 32 degrees C, whereas the rest were maintained at 21 degrees C. Control sedentary rats yoked to ABA animals received the same treatment. ABA rats (21 degrees C) showed increased Melanocortin 4 (MC4) receptor and Agouti gene Related Peptide (AgRP) expression, and decreased pro-opiomelanocortin (POMC) mRNA levels (Real Time PCR), with respect to controls. Heat application increased weight gain and food intake, and reduced running rate in ABA rats, when compared with ABA rats at 21 degrees C. However, no changes in body weight and food intake were observed in sedentary rats exposed to heat. Moreover, heat application reduced MC4 receptor, AgRP and POMC expression in ABA rats, but no changes were observed in control rats. These results indicate that hypothalamic MC4 receptor overexpression could occur on the basis of the characteristic hyperactivity, weight toss, and self-starvation of ABA rats, and suggest the involvement of hypothalamic melanocortin neural circuits in behavioural changes shown by AN patients. Changes in AgRP and POMC expression could represent an adaptative response to equilibrate energy balance. Moreover, the fact that HAT reversed hypothalamic MC4 receptor overexpression in ABA rats indicates the involvement of brain melanocortin system in the reported beneficial effects of heat application in AN. A combination of MC4 receptor antagonists and heat application could improve the clinical management of AN. (C) 2008 Elsevier Ltd. All rights reserved.