室旁核的NUCB2/nesfatin-1是瘦素的直接作用靶点，并介导其厌食作用。
Paraventricular NUCB2/nesfatin-1 is directly targeted by leptin and mediates its anorexigenic effect.
作者信息
Darambazar Gantulga, Nakata Masanori, Okada Takashi, Wang Lei, Li EnXu, Shinozaki Atsumi, Motoshima Megumi, Mori Masatomo, Yada Toshihiko
机构信息
Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
出版信息
Biochem Biophys Res Commun. 2015 Jan 24;456(4):913-8. doi: 10.1016/j.bbrc.2014.12.065. Epub 2014 Dec 19.
An adipokine leptin plays a central role in the regulation of feeding and energy homeostasis via acting on the hypothalamus. However, its downstream neuronal mechanism is not thoroughly understood. The neurons expressing nucleobindin-2 (NUCB2)-derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) have been implicated in feeding and energy homeostasis. The present study aimed to explore the role of PVN NUCB2/nesfatin-1 in the leptin action, by using adeno-associated virus (AAV) vectors encoding shRNA targeting NUCB2 (AAV-NUCB2-shRNA). Leptin directly interacted and increased cytosolic Ca(2+) in single neurons isolated from the PVN, predominantly in NUCB2/nesftin-1-immunoreactive neurons. Treatment with leptin in vivo and in vitro markedly increased NUCB2 mRNA expression in the PVN. Peripheral and central injections of leptin failed to significantly inhibit food intake in mice receiving AAV-NUCB2. These results indicate that PVN NUCB2/nesfatin-1 is directly targeted by leptin, and mediates its anorexigenic effect.
脂肪因子瘦素通过作用于下丘脑在进食和能量稳态调节中发挥核心作用。然而，其下游神经元机制尚未完全阐明。下丘脑室旁核（PVN）中表达核结合蛋白2（NUCB2）衍生的nesfatin-1的神经元与进食和能量稳态有关。本研究旨在通过使用编码靶向NUCB2的短发夹RNA（shRNA）的腺相关病毒（AAV）载体，探讨PVN NUCB2/nesfatin-1在瘦素作用中的作用。瘦素直接与从PVN分离的单个神经元相互作用并增加其胞质Ca(2+)，主要是在NUCB2/nesftin-1免疫反应性神经元中。体内和体外给予瘦素治疗均显著增加PVN中NUCB2 mRNA的表达。对接受AAV-NUCB2的小鼠进行外周和中枢注射瘦素未能显著抑制其食物摄入。这些结果表明，PVN NUCB2/nesfatin-1是瘦素的直接作用靶点，并介导其厌食作用。
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