Satoh N, Ogawa Y, Katsuura G, Numata Y, Masuzaki H, Yoshimasa Y, Nakao K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Neurosci Lett. 1998 Jun 19;249(2-3):107-10. doi: 10.1016/s0304-3940(98)00401-7.
Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.
瘦素是一种由脂肪细胞产生、通过血液传输的饱腹感因子，它能减少食物摄入量并增加能量消耗，从而导致体重显著下降。为了探究下丘脑黑皮质素系统在瘦素作用中的可能作用，我们研究了向大鼠脑室内（i.c.v.）注射瘦素，以及注射瘦素时联合或不联合注射α-黑素细胞刺激素的强效拮抗剂SHU9119，对大鼠食物摄入量、体重以及棕色脂肪组织（BAT）中线粒体解偶联蛋白-1（UCP-1）mRNA表达的影响。单次脑室内注射瘦素可减少累积食物摄入量和体重增加，并在黑暗期开始后的3小时内增加UCP-1 mRNA表达。联合注射SHU9119可剂量依赖性地逆转瘦素对食物摄入量和体重变化的抑制作用。联合注射SHU9119还完全抑制了瘦素诱导的BAT中UCP-1 mRNA表达的增加。单独使用SHU9119处理对大鼠的食物摄入量、体重和UCP-1 mRNA表达没有影响。本研究提供了证据，表明下丘脑黑皮质素系统在瘦素的饱腹感效应和交感神经激活中均起核心作用。
