Research on the molecular neural mechanism of appetite nerve modulation by chronic fatigue

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K20136
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kyoto Tachibana University (2022); Institute of Physical and Chemical Research (2019-2021)
• Principal Investigator: hu di 京都橘大学, 健康科学部, 助教C (60758580)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 慢性疲労 / レプチン / グレリン / ストレス / 内分泌調節

Outline of Final Research Achievements

To elucidate the mechanism of chronic fatigue formation, we developed a unique animal model. Immediately after fatigue loading, blood ghrelin was elevated and leptin was markedly decreased. Blood ACTH and a-MSH were also elevated. The elevated ghrelin inhibited the POMC nerve in the hypothalamus, but the elevated ACTH/a-MSH downstream of the POMC after the fatigue load indicated the failure of ghrelin to inhibit the POMC nerve, suggesting the possibility of abnormal regulatory function. Furthermore, leptin supplementation in a leptin-depleted animal model significantly restored the amount of spontaneous behavior. Since leptin can freely cross the cerebral blood barrier, the results suggest that improved recovery from fatigue by supplementation may correct the modulation of central appetite control and prevent chronic fatigue even with peripheral intervention.

Free Research Field

行動生理学

Academic Significance and Societal Importance of the Research Achievements

本研究で使用した慢性疲労モデルにおいて、血中グレリンの顕著な増加、レプチンの低下、さらにACTHとa-MSHの上昇も認められた。食欲制御中枢では、グレリン増加によるACTHとa-MSHのネガティブフィードバックが作動しなかったことは、長期疲労負荷が原因と考えられ、食欲制御の異常が疲労の慢性化形成に密接な関係が明らかになった。レプチンの補充による自発行動量の有意な改善が、食欲中枢制御の異常是正によるもので、末梢のレプチン介入治療が慢性疲労症候群を改善・予防する可能性が示された。本研究の成果は、慢性疲労症候群の診断・予防・治療法の開発を大きく前進させ、疲労克服社会を実現する基盤を築く。