The rhythmic activity of neurons in arcuate nucleus and paraventricular nucleus regulate feeding behavior and metabolism.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Wakayama Medical University (2018); Jichi Medical University (2015-2017)
• Principal Investigator: Nakata Masanori 和歌山県立医科大学, 医学部, 教授 (10305120)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 摂食行動 / 室傍核 / Nesfatin-1 / FGF21 / メタボリックシンドローム / 弓状核 / 概日リズム

Outline of Final Research Achievements

Nesfatin-1, an anorectic peptide processed from nucleobindin-2 (NUCB2), is expressed in the hypothalamus including the paraventricular nucleus (PVN). PVN specific NUCB2 knockdown induces LP-selective hyperphagia and reduction of PVN Oxt mRNA expression as early as 3-4 weeks after AAV treatment, which were followed by increases in daily food intake and body weight in later period. These results reveal that the endogenous nesfatin-1 neuron in PVN regulates PVN oxytocin and consequently the energy balance. Furthermore, we clarified that fibroblast growth factor (FGF) 21 is a novel regulator of nesfatin-1 neurons. ICV injection of FGF21 markedly suppressed food intake in fed mice with elevated blood glucose. FGF21 failed to suppress food intake in PVN-preferential Nucb2 knockout mice. These results demonstrate that the PVN nesfatin-1 neurons physiologically sense key peripheral metabolic signals, and thereby regulate circadian feeding rhythm and glucose metabolism.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

生活リズムの乱れ、特に食行動リズムの乱れは生活習慣病を増悪させる。食行動リズムの形成機構を解明することは、生活習慣病の病態の解明および予防・治療に有用である。本研究では、食行動リズムは、室傍核Nesfatin1ニューロンの活動リズムが制御する事を示した。さらにNesfatin-1ニューロンの上流はFGF21、下流はOxytocinニューロンである事も示した。この結果から、FGF21、Nesfatin-1、Oxytocinを標的とした生活習慣病の予防・治療法確立への展開が期待できる。さらに、弓状核-室傍核軸を切り口として血圧制御機構の分子基盤を与え、治療介入点を示すことが出来た。