The injection of a melanocortin peptide or of melanocortin peptide analogues into the cerebrospinal fluid or into the ventromedial hypothalamus in nanomolar or subnanomolar doses induces a long-lasting inhibition of food intake. The effect keeps significant for up to 9 h and has been observed in all animal species so far tested, the most susceptible being the rabbit. The anorectic effect of these peptides is a primary one, not secondary to the shift towards other components of the complex melanocortin-induced behavioral syndrome, in particular grooming. The site of action is in the brain, and the effect is not adrenal-mediated because it is fully exhibited also by adrenalectomized animals. It is a very strong effect, because the degree of feeding inhibition is not reduced in conditions of hunger, either induced by 24 h starvation, or by insulin-induced hypoglycemia, or by stimulation of gamma-aminobutyric acid (GABA), noradrenergic or opioid systems. The microstructural analysis of feeding behavior suggests that melanocortins act as satiety-inducing agents, because they do not significantly modify the latencies to start eating, but shorten the latencies to stop eating. The mechanism of action involves the activation of melanocortin MC(4) receptors, because selective melanocortin MC(4) receptor antagonists inhibit the anorectic effect of melanocortins, while inducing per se a strong stimulation of food intake and a significant increase in body weight. Melanocortins seem to play an important role in stress-induced anorexia, because such condition, in rats, is significantly attenuated by the blockage of melanocortin MC(4) receptors; such a role is not secondary to an increased release of corticotropin-releasing factor (CRF), because, on the other hand, the CRF-induced anorexia is not affected at all by the blockage of melanocortin MC(4) receptors. The physiological meaning of the feeding inhibitory effect of melanocortins, and, by consequence, the physiological role of melanocortins in the complex machinery responsible for body weight homeostasis, is testified by the hyperphagia/obesity syndromes caused by mutations in the pro-opiomelanocortin (POMC) gene, or in the melanocortin MC(4) receptor gene, or in the agouti locus. Finally, recent evidences suggest that melanocortins could be involved in mediating the effects of leptin, and in controlling the expression of neuropeptide Y (NPY).

译文

以纳摩尔或亚纳摩尔剂量将黑皮质素肽或黑皮质素肽类似物注射到脑脊液或腹内侧下丘脑中,可长期抑制食物摄入。这种作用在长达9小时内保持显着,并且到目前为止已在所有测试的动物物种中观察到,最易感的是兔子。这些肽的厌食作用是主要的,而不是继发于向复杂的黑皮质素诱导的行为综合征的其他成分的转变,尤其是修饰。作用部位在大脑中,并且该作用不是肾上腺介导的,因为肾上腺切除的动物也完全表现出它。这是非常强烈的作用,因为在饥饿条件下,由于24小时饥饿或胰岛素诱导的低血糖或通过刺激 γ-氨基丁酸 (GABA),去甲肾上腺素能或阿片类药物系统。喂养行为的微观结构分析表明,黑色素可作为饱腹感的诱导剂,因为它们不会显着改变开始进食的潜伏期,但会缩短停止进食的潜伏期。作用机制涉及黑皮质素MC(4) 受体的激活,因为选择性黑皮质素MC(4) 受体拮抗剂抑制黑皮质素的厌食作用,同时诱导本身对食物摄入的强烈刺激和体重的显着增加。黑素皮质激素似乎在应激诱导的厌食症中起重要作用,因为在大鼠中,黑素皮质激素MC(4) 受体的阻断可显着减弱这种状况; 这种作用并非继发于促肾上腺皮质激素释放因子 (CRF) 的释放增加,因为另一方面,CRF诱导的厌食症完全不受黑皮质素MC(4) 受体阻断的影响。黑素皮质素的摄食抑制作用的生理意义,以及黑素皮质素在负责体重稳态的复杂机器中的生理作用,由亲鸦片黑素皮质素 (POMC) 基因突变引起的食欲亢进/肥胖综合征证明。或在黑皮质素MC(4) 受体基因中,或在agouti基因座中。最后,最近的证据表明,黑素皮质激素可能参与介导瘦素的作用,并控制神经肽Y (NPY) 的表达。

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