BBRC：日本研究人员揭示大脑如何调节食欲

日本自治医科大学教授矢田俊彦率领的研究小组日前宣布，他们发现了人体进食后部分物质如何使大脑产生吃饱的感觉。进一步的研究有望让研究人员开发出新疗法治疗暴食和肥胖等病症。

此前的研究已发现，人体进食时，在作为食欲中枢的丘脑下部室旁核中，一种称为“nesfatin-1”的蛋白质会增加，让人产生吃饱感。但具体机制如何运作一直是个谜。

研究人员在小鼠身上进行实验来探究这一机制，他们从小鼠的室旁核中取出脑神经细胞，标定了一些含有“nesfatin-1”蛋白质的细胞，并发现这种细胞能与高浓度的葡萄糖和胰岛素发生反应并被激活。由于人们进食米饭和面包等碳水化合物后，血液中的葡萄糖和胰岛素的浓度会增加，因此上述的反应可能是大脑产生吃饱感的部分原因。

研究小组3月24日在线发表于《生物化学和生物物理研究通讯》（Biochemical and Biophysical Research Communications）上的论文指出，如果今后能弄清蛋白质的氨基酸和类脂化合物对吃饱感有何影响，以及进食时间不同导致的吃饱感差异，就有望开发出新疗法对暴食、肥胖等病症进行有效治疗。（生物谷 bioon.com）

doi:10.1016/j.bbrc.2012.03.079
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Glucose and insulin induce Ca²⁺ signaling in nesfatin-1 neurons in the hypothalamic paraventricular nucleus

Darambazar Gantulga, , Yuko Maejima, , Masanori Nakata, , Toshihiko Yada

Nucleobindin-2 derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) plays a role in inhibition of feeding. The neural pathways downstream of PVN nesfatin-1 have been extensively investigated. However, regulation of the PVN nesfatin-1 neurons remains unclear. Since starvation decreases and refeeding stimulates nesfatin-1 expression specifically in the PVN, this study aimed to clarify direct effects of meal-evoked metabolic factors, glucose and insulin, on PVN nesfatin-1 neurons. High glucose (10 mM) and insulin (10?13 M) increased cytosolic calcium concentration ([Ca2+]i) in 55 of 331 (16.6%) and 32 of 249 (12.9%) PVN neurons, respectively. Post [Ca2+]i measurement immunocytochemistry identified that 58.2% of glucose-responsive and 62.5% of insulin-responsive neurons were immunoreactive to nesfatin-1. Furthermore, a fraction of the glucose-responsive nesfatin-1 neurons also responded to insulin, and vice versa. Some of the neurons that responded to neither glucose nor insulin were recruited to [Ca2+]i increases by glucose and insulin in combination. Our data demonstrate that glucose and insulin directly interact with and increase [Ca2+]i in nesfatin-1 neurons in the PVN, and that the nesfatin-1 neuron is the primary target for them in the PVN. The results suggest that high glucose- and insulin-induced activation of PVN nesfatin-1 neurons serves as a mechanism through which meal ingestion stimulates nesfatin-1 neurons in the PVN and thereby produces satiety.