Jethwa Preeti H, Small Caroline J, Smith Kirsty L, Seth Asha, Darch Sarah J, Abbott Caroline R, Murphy Kevin G, Todd Jeannie F, Ghatei Mohammad A, Bloom Stephen R
Dept. of Metabolic Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E301-5. doi: 10.1152/ajpendo.00404.2004. Epub 2005 Mar 22.
Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for </=8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 +/- 2.0 g; leptin, 13.7 +/- 2.3 g (P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 +/- 1.3 g (P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 +/- 4.9 g; leptin, 20.8 +/- 2.6 g (P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 +/- 1.1 g (P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety.
脑室内（ICV）注射神经介素U（NMU，一种下丘脑神经肽）或瘦素（一种由脂肪组织释放的脂肪稳态激素）可减少食物摄入量并增加能量消耗。瘦素在体外刺激NMU的释放，而在瘦素水平低或缺乏的模型中，NMU表达降低。我们研究了NMU在介导瘦素诱导的饱腹感中的作用。给饱腹大鼠脑室内注射抗NMU免疫球蛋白G（IgG）（5 nmol），注射后4小时食物摄入量显著增加，这种效应在注射后≤8小时可见。给禁食大鼠脑室内注射NMU（1 nmol），与对照组相比，注射后1小时食物摄入量减少，抗NMU IgG预处理可减弱这种效应。脑室内注射瘦素（0.625 nmol）可减少24小时食物摄入量。抗NMU IgG给药可部分减弱这种效应[黑暗期开始后24小时：载体，22.5±2.0克；瘦素，13.7±2.3克（与载体相比，P<0.005），瘦素/NMU IgG，19.4±1.3克（与瘦素相比，P<0.05）]。腹腔注射瘦素（1.1毫克/千克体重）可减少24小时食物摄入量。脑室内注射抗NMU IgG可部分减弱这种效应[黑暗期开始后24小时：载体，31.4±4.9克；瘦素，20.8±2.6克（与载体相比，P<0.01）；瘦素/NMU IgG，28.7±1.1克（与瘦素相比，P<0.01）]。这些结果表明，NMU在食欲调节中发挥生理作用，并部分介导瘦素诱导的饱腹感。
