Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA.
J Neuroendocrinol. 2012 Jul;24(7):1078-84. doi: 10.1111/j.1365-2826.2012.02304.x.
Nesfatin-1, a post-translational product of the nucleobindin-2 (NucB2) gene, is produced in several brain areas known to be important in neuroendocrine, autonomic and metabolic function, including the hypothalamus and medulla. The hallmark action of the peptide is its ability at picomole doses to inhibit food and water intake in rodents and, indeed, the effect on water intake is more pronounced than that on food intake. In preliminary studies, we observed a decrease in hypothalamic NucB2 expression in response to overnight water deprivation even when food was present, which reversed when water was returned to the animals. We therefore hypothesised that the effect of nesfatin-1 on water drinking was independent of its anorexigenic action. Indeed, rats administered nesfatin-1 i.c.v. consumed significantly less water than controls in response to a subsequent, dipsogenic dose of angiotensin II, or upon return of water bottles after 18 h of fluid restriction (food present), or in response to a hypertonic challenge. Pretreatment with an antisense oligonucleotide against nesfatin-1 significantly reduced levels of immunoreactive nesfatin-1 in the hypothalamic paraventricular nucleus and resulted in exaggerated drinking responses to angiotensin II. The results obtained in the present study suggest that locally produced nesfatin-1 may be an important component of the hypothalamic mechanisms controlling fluid and electrolyte homeostasis.
nesfatin-1 是核结合蛋白 2（NucB2）基因的翻译后产物，存在于多个脑区，这些脑区已知在神经内分泌、自主和代谢功能中发挥重要作用，包括下丘脑和延髓。该肽的主要作用是能够在皮摩尔剂量下抑制啮齿动物的食物和水摄入，事实上，其对水摄入的影响比对食物摄入的影响更为明显。在初步研究中，我们观察到，即使有食物存在，隔夜水剥夺也会导致下丘脑 NucB2 表达减少，而当水返回动物体内时，这种表达减少会得到逆转。因此，我们假设 nesfatin-1 对水摄入的影响与其抑制食欲的作用无关。事实上，给予 nesfatin-1 脑室注射的大鼠在接受随后的血管紧张素 II 致渴剂量或在经过 18 小时液体限制（有食物）后水瓶返回时，或在高渗性挑战时，与对照组相比，摄水量明显减少。用 nesfatin-1 的反义寡核苷酸预处理显著降低了下丘脑室旁核中免疫反应性 nesfatin-1 的水平，并导致对血管紧张素 II 的饮水反应过度。本研究的结果表明，局部产生的 nesfatin-1 可能是调节液体和电解质平衡的下丘脑机制的重要组成部分。
