Molecular mechanism in the brain of the change in food preference associated with rapid weight loss after obesity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11079
• 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: University of the Ryukyus
• Principal Investigator: Okamoto Shiki 琉球大学, 医学(系)研究科(研究院), 助教 (40342919)
• Co-Investigator(Kenkyū-buntansha): 益崎 裕章 琉球大学, 医学(系)研究科(研究院), 教授 (00291899)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 炭水化物嗜好性 / CRH / 肥満 / リバウンド

Outline of Final Research Achievements

It is well known that rapid weight loss is accompanied by picky eating and abnormal eating behavior, which may lead to a rebound, but detailed molecular mechanisms in the brain remain unclear. In the present study, we focused on changes in food preference and analyzed the mechanisms that regulate abnormal eating behavior in the hypothalamus during different periods of weight change. In the post-obesity weight-loss mice (WL), fat intake increased in addition to carbohydrate intake, resulting in an increase in total caloric intake. In the paraventricular nucleus of the WL mice, the expression of fatty acid metabolism genes was increased in addition to several ion channels and neuropeptide receptors, but arachidonic acid metabolism genes were strongly suppressed. We are now analyzing feeding behavior after expression modification using viral vectors encoding these candidate genes for obese memory, and are investigating the regulatory mechanisms in detail.

Free Research Field

神経内分泌学

Academic Significance and Societal Importance of the Research Achievements

ストレス応答ホルモンであるCRHが惹起する炭水化物嗜好性変化は、生体の糖エネルギー需要を鋭敏に反映する。肥満に続く急激な減量時における新規神経ネットワークでは、ストレスによる急激な生体内環境変化におけるアンバランスなエネルギー調節機構を制御仕切れない可能性が高い。減量時の生体内エネルギー需要を嗜好性変化に着目して精確に検知し、適切な時期にCRHニューロン活動を制御することにより、摂食行動異常を是正する研究に発展させ摂食障害に対する新規ターゲット療法の確立につながると確信する。