Department of Clinical Medicine, Sapienza University of Rome, Italy.
Curr Opin Support Palliat Care. 2010 Dec;4(4):249-53. doi: 10.1097/SPC.0b013e32833e4aa5.
Anorexia is a severe debilitating symptom characterizing the clinical course of several chronic diseases. It negatively impacts on patient outcome by contributing to weight loss, lean body mass catabolism and adipose tissue wasting. Although disease-associated anorexia may stand alone as a clinically relevant symptom, it is now considered as a component of the cachexia syndrome. The present review discusses experimental and clinical data indicating that the pathogenic mechanisms of anorexia may also suggest a neural control of tissue wasting in cachexia.
Consistent data show that selective melanocortin receptor antagonism modulates food intake and reduces wasting in experimental models of chronic disease. Consequently, ghrelin administration, whose prophagic effects are related to melanocortin antagonism, has been tested both in animal studies and human trials, with promising effects, although restoration of lean body mass has been not achieved. More interest is driven by the use of small molecules selectively antagonising hypothalamic melanocortin receptors.
The 'brain-muscle axis' coordinated by the hypothalamus seems to mediate the onset of not only anorexia but also tissue wasting in cachexia, by centrally influencing energy homeostasis and the balance between anabolism and catabolism.
厌食是几种慢性疾病临床过程中的严重致残症状。它通过导致体重减轻、去脂体重分解和脂肪组织消耗,对患者的预后产生负面影响。虽然与疾病相关的厌食症可能单独作为一个有临床意义的症状存在,但现在它被认为是恶病质综合征的一个组成部分。本文综述讨论了实验和临床数据,这些数据表明厌食症的发病机制也可能提示恶病质中组织消耗的神经控制。
一致的数据表明,选择性黑皮质素受体拮抗剂可调节食物摄入并减少慢性疾病动物模型中的消耗。因此,ghrelin 的给药,其促进摄食的作用与黑皮质素拮抗作用有关,已经在动物研究和人体试验中进行了测试,结果有一定的效果,尽管未能恢复瘦体重。人们对选择性拮抗下丘脑黑皮质素受体的小分子的使用更感兴趣。
由下丘脑协调的“脑-肌肉轴”似乎通过中枢影响能量平衡和合成代谢与分解代谢之间的平衡,不仅介导厌食症的发生,而且介导恶病质中组织消耗的发生。