Peripheral Administration of Nesfatin-1 Reduces Food Intake in Mice: The Leptin-Independent Mechanism
Peripheral Administration of Nesfatin-1 Reduces Food Intake in Mice: The Leptin-Independent Mechanism
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DOI：
10.1210/en.2008-0598
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发表时间：
2009-02-01
期刊：
影响因子：
4.8
通讯作者：
Mori, M.
中科院分区：
文献类型：
--
作者：
Shimizu, H.;Oh-I, S.;Mori, M.
Nesfatin-1是下丘脑中的一种新的饱腹感分子，也存在于外周组织中。在这里，我们试图鉴定奈法丁-1的活性片段，并确定其在小鼠外周给药后的作用机制。腹膜内注射nesfatin-1抑制食物摄入的剂量依赖性方式。Nesfatin-1有三个不同的片段;我们测试了每个片段对食物摄入的影响。在瘦素抵抗条件下，如db/db小鼠和高脂饮食小鼠，注射中段减少了食物摄入。注射中段后，c-Fos在脑干孤束核（NTS）中的表达显着激活，但在下丘脑弓状核中没有激活;通往NTS的尼古丁胆碱能途径导致中段诱导的厌食症。中段注射显着增加表达的前阿黑皮素和可卡因和安非他明调节的转录基因在NTS，但不是在弓状核。对突变体中间片段的研究表明，与刺豚鼠相关肽活性位点氨基酸序列相似的区域对于刺豚鼠毒素诱导是必不可少的。我们的研究结果表明，nesfatin-1的中段引起厌食症，可能是通过激活POMC和CART神经元在NTS通过瘦素独立的机制后，外周刺激。（内分泌学150：662-671，2009）
Nesfatin-1 is a novel satiety molecule in the hypothalamus and is also present in peripheral tissues. Here we sought to identify the active segment of nesfatin-1 and to determine the mechanisms of its action after peripheral administration in mice. Intraperitoneal injection of nesfatin-1 suppressed food intake in a dose-dependent manner. Nesfatin-1 has three distinct segments; we tested the effect of each segment on food intake. Injection of the midsegment decreased food intake under leptin-resistant conditions such as db/db mice and mice fed a high-fat diet. After injection of the midsegment, expression of c-Fos was significantly activated in the brainstem nucleus tractus solitarius (NTS) but not in the hypothalamic arcuate nucleus; the nicotinic cholinergic pathway to the NTS contributed to midsegment-induced anorexia. Midsegment injection significantly increased expression of proopiomelanocortin and cocaine- and amphetamine-regulated transcript genes in the NTS but not in the arcuate nucleus. Investigation of mutant midsegments demonstrated that a region with amino acid sequence similarity to the active site of agouti-related peptide was indispensable for anorexigenic induction. Our findings indicate that the midsegment of nesfatin-1 causes anorexia, possibly by activating POMC and CART neurons in the NTS via a leptin-independent mechanism after peripheral stimulation. (Endocrinology 150: 662-671, 2009)