Gutiérrez E, Churruca I, Zárate J, Carrera O, Portillo M P, Cerrato M, Vázquez R, Echevarría E
Departments of Clinical Psychology and Psychobiology, University of Santiago de Compostela, Spain.
Psychoneuroendocrinology. 2009 Apr;34(3):420-9. doi: 10.1016/j.psyneuen.2008.10.003. Epub 2008 Nov 20.
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 loss, 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.
研究了黑皮质素系统在基于活动的厌食（ABA）大鼠（神经性厌食症（AN）的类似模型）中热疗有益作用中的潜在参与情况。一旦ABA大鼠体重减轻20%，将一半动物暴露于32摄氏度的高环境温度（HAT）下，而其余动物维持在21摄氏度。与ABA动物配对的对照久坐大鼠接受相同处理。与对照组相比，ABA大鼠（21摄氏度）的黑皮质素4（MC4）受体和刺鼠基因相关肽（AgRP）表达增加，促阿片黑素皮质素原（POMC）mRNA水平降低（实时定量PCR）。与21摄氏度的ABA大鼠相比，热疗增加了ABA大鼠的体重增加和食物摄入量，并降低了奔跑速度。然而，暴露于热环境的久坐大鼠体重和食物摄入量没有变化。此外，热疗降低了ABA大鼠中MC4受体、AgRP和POMC的表达，但对照大鼠未观察到变化。这些结果表明，下丘脑MC4受体过表达可能基于ABA大鼠的特征性多动、体重减轻和自我饥饿而发生，并提示下丘脑黑皮质素神经回路参与AN患者表现出的行为变化。AgRP和POMC表达的变化可能代表一种平衡能量平衡的适应性反应。此外，HAT逆转了ABA大鼠下丘脑MC4受体过表达这一事实表明，脑黑皮质素系统参与了热疗对AN的有益作用。MC4受体拮抗剂与热疗联合应用可能改善AN的临床管理。
