Elucidation of the mechanism underlying the regulation of food-entrained feeding rhythm

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Gifu University
• Principal Investigator: Umehara Hayato 岐阜大学, 大学院医学系研究科, 准教授 (20610182)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 摂食リズム / 条件給餌 / 摂餌予知行動 / ヒスタミン神経系

Outline of Final Research Achievements

When mice were subjected to a scheduled feeding in which food availability is restricted for a few hours in a day, they develop food-anticipatory activity (FAA) but the mechanism underlying the daily food-anticipation remains elusive. The author demonstrated a part of histaminergic neurons were activated synchronizing the circadian rhythm of food-anticipation. In addition, injection of anti-histaminergic drugs prior to the daily mealtime reduced FAA as well as activity of downstream neurons that receive projection of the histaminergic neurons. In addition, gene expressions of histamine-producing enzyme, and of histamine receptor at the projection site showed dynamic changes correspondingly with the rhythm of the histaminergic activity, in a pilot study. These data suggest that the histaminergic neurons play a role in the regulation of food-anticipation through H1R via specific histaminergic circuit.

Free Research Field

神経科学、薬理学

Academic Significance and Societal Importance of the Research Achievements

日々の摂食時刻を予知する摂餌予知行動は明らかな概日リズムを示す。このリズムは既知の体内時計を破壊しても消失しないことから、第2の体内時計の存在が示唆されてきた。しかし、未だその本体は明らかとなっていない。本研究は摂餌予知行動のリズムを生み出す仕組みの一端を解明することとなり、未知の生体時計の解明につながる可能性がある（学術的意義）。
一方、摂食リズムの破綻は肥満の危険因子として知られ、正常な摂食リズムの制御機構の解明は、その異常により引き起こされる病態の病理機構解明にもつながりうる。したがって、本研究の成果は今後肥満やそれに伴う病態の新たな治療戦略の構築に役立つ可能性がある（社会的意義）。