Frontier Science Research Center, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Endocrinology. 2010 May;151(5):2200-10. doi: 10.1210/en.2009-1153. Epub 2010 Feb 26.
Neuropeptide W (NPW) is an anorectic peptide produced in the brain. Here, we showed that NPW was present in several hypothalamic nuclei, including the paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, lateral hypothalamus, and hypothalamic arcuate nucleus. NPW expression was significantly up-regulated in leptin-deficient ob/ob and leptin receptor-deficient db/db mice. The increase in NPW expression in ob/ob mice was abrogated to control levels after leptin replacement. Leptin induced suppressors of cytokine signaling-3 after phosphorylation of signal transducer and activator of transcription-3 in NPW-expressing neurons. In addition, we demonstrated that NPW reduces feeding via the melanocortin-4-receptor signaling pathway. We also showed that NPW activates proopiomelanocortin and inhibits neuropeptide Y neurons using loose-patch extracellular recording of these neurons identified by promoter-driven green fluorescent protein expression. This study indicates that NPW may play an important role in the regulation of feeding and energy metabolism under the conditions of leptin insufficiency.
神经肽 W（NPW）是一种在大脑中产生的厌食肽。在这里，我们表明 NPW 存在于几个下丘脑核中，包括室旁下丘脑核、腹内侧下丘脑核、外侧下丘脑核和下丘脑弓状核。瘦素缺乏型 ob/ob 和瘦素受体缺乏型 db/db 小鼠中 NPW 的表达明显上调。瘦素替代后，ob/ob 小鼠中 NPW 表达的增加被阻断至对照水平。瘦素诱导信号转导和转录激活因子 3 磷酸化后抑制细胞因子信号转导抑制物 3 在 NPW 表达神经元中。此外，我们证明 NPW 通过黑素皮质素-4-受体信号通路减少摄食。我们还使用通过启动子驱动的绿色荧光蛋白表达鉴定的这些神经元的松散贴片细胞外记录表明，NPW 激活前阿黑皮素原并抑制神经肽 Y 神经元。这项研究表明，在瘦素不足的情况下，NPW 可能在调节摄食和能量代谢中发挥重要作用。
