Identification of nesfatin-1 as a satiety molecule in the hypothalamus
Identification of nesfatin-1 as a satiety molecule in the hypothalamus
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DOI：
10.1038/nature05162
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发表时间：
2006-10-12
期刊：
影响因子：
64.8
通讯作者：
Mori, Masatomo
中科院分区：
文献类型：
--
作者：
Oh-, Shinsuke, I;Shimizu, Hiroyuki;Mori, Masatomo
大脑下丘脑含有某些在调节摄食行为中起重要作用的分泌分子（1-3）。在这里，我们发现nesfatin，对应于NEFA/nucleobindin(2) (NUCB2)，一种功能未知的分泌蛋白，在大鼠食欲控制的下丘脑核中表达。脑室内注射NUCB2可减少摄食。大鼠脑脊液中含有nesfatin-1，这是一种源自NUCB2的氨基末端片段，在饥饿条件下，其在下丘脑室旁核中的表达减少。静脉注射nesfatin-1以剂量依赖的方式减少食物摄入量，而注射中和nesfatin-1的抗体则刺激食欲。相比之下，c.c.v注射其他可能由NUCB2加工而来的片段不能促进饱腹感，而NUCB2转化为巢脂素-1是诱导摄食抑制的必要条件。慢性体外注射nesfatin-1可使大鼠体重减轻，而慢性体外注射针对NUCB2基因编码的反义morpholino寡核苷酸可使大鼠体重增加。nesfatin-1诱导的厌食症发生在瘦素受体突变的Zucker大鼠中，抗nesfatin-1抗体不能阻断瘦素诱导的厌食症。相反，中枢注射α -黑素细胞刺激激素可提高室旁核中NUCB2基因的表达，nesfatin-1的饱腹感被黑素皮质素3/4受体拮抗剂消除。我们发现nesfatin-1是一种与下丘脑黑素皮质素信号相关的饱腹感分子。
The brain hypothalamus contains certain secreted molecules that are important in regulating feeding behaviour(1-3). Here we show that nesfatin, corresponding to NEFA/nucleobindin(2) (NUCB2), a secreted protein of unknown function, is expressed in the appetite-control hypothalamic nuclei in rats. Intracerebroventricular (i.c.v.) injection of NUCB2 reduces feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.