Mechanism on efffect of anti-obesity by chrebp deficiency

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K01883
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Hyogo Medical University
• Principal Investigator: sakiyama haruhiko 兵庫医科大学, 医学部, 講師 (30508958)
• Co-Investigator(Kenkyū-buntansha): 鈴木 敬一郎 兵庫医科大学, 医学部, 教授 (70221322) ; 江口 裕伸 兵庫医科大学, 医学部, 講師 (60351798) ; 吉原 大作 兵庫医科大学, 医学部, 助教 (00567266) ; 藤原 範子 兵庫医科大学, 医学部, 教授 (10368532)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ChREBP / 転写因子 / スクラーゼ

Outline of Final Research Achievements

The glucose　responsive transcription factor ChREBP regulates the expression levels of enzymes related to glycolysis and lipogenesis by translocating into the nucleus according to glucose concentration. Once ChREBP is activated, glycolysis and fatty acid synthesis are accelerated. In ChREBP KO mice, it is considered that obesity is unlikely to occur due to the relative decrease in these metabolisms. In brown adipose tissue, in addition to decreased metabolism, the expression level of uncoupling protein1 (UCP1) involved in fat burning was increased. Therefore, even if fat is accumulated, it is quickly decomposed, and it is considered that weight is unlikely to increase.　Therefore, if the activation of ChREBP can be suppressed, it is expected to be useful for the treatment and prevention of metabolic syndrome.

Free Research Field

糖・脂質代謝

Academic Significance and Societal Importance of the Research Achievements

肥満や糖尿病を含めたメタボリックシンドロームは社会問題となっている。転写因子ChREBPの活性化はこれら病態の亢進に深く関与していることが分かってきた。そこでChREBP KOマウスの特徴である抗肥満作用のメカニズムを解明することで、ChREBPをターゲットとした治療薬の開発につなげようと試みている。ChREBPの阻害剤が開発されればメタボリックシンドロームの予防や治療に役立つことが大いに期待される。