Analysis of hunger and satiety signalling pathway from peripheral to central nervous system using visualizing technology of a marker of neuronal activation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Hokkaido University
• Principal Investigator: Hisadome Kazunari 北海道大学, 歯学研究院, 助教 (00592081)
• Co-Investigator(Kenkyū-buntansha): 舩橋 誠 北海道大学, 歯学研究院, 教授 (80221555)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 摂食調節

Outline of Final Research Achievements

Glucagon-like peptide-1 (GLP-1) is released postprandially from the gut and known as a satiety peptide. However, it’s unclear whether peripheral GLP-1 can directly reach receptors in the brain. To examine how peripheral GLP-1 reaches into the brain, we analyzed the c-Fos, a marker of neuronal activation, expression in the brainstem neurons after intraportal injection of GLP-1. Physiological concentration of GLP-1 induced c-Fos expression of nucleus tract solitarius neurons, but not of area postrema neurons. These results suggest the GLP-1 secreted from the gut might reach the brain as a signal via vagal nerve rather than as a hormone via the bloodstream. These experiments were used transgenic rat expressing green fluorescent protein (GFP) under control of a c-fos promoter. Therefore, c-Fos-expressing neurons were identifiable by GFP. This experimental design might be applicable to the identification of secondary neurons for satiety- or hunger-signal of peripheral peptides.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

これまで、困難とされていた末梢刺激に対して応答を示した中枢神経の神経細胞を生細胞の状態で同定できることから、末梢刺激から中枢神経投射後の神経ネットワーク解析まで一連の求心性伝達系を連続的に解析できる汎用性の高い結果が得られた。
また、食欲調節に関わる情報伝達の詳細な機序を明らかにできる可能性を有していることから、社会的問題とされれる肥満や拒食の治療法へつながる研究結果と考えられる。