Clarification of the inter-organ mechanism regulating metabolism of nutrients

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02858
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Teikyo University
• Principal Investigator: Uno Kenji 帝京大学, 医学部, 准教授 (50596632)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 糖代謝 / 脂質代謝 / アミノ酸代謝 / 臓器間ネットワーク / 糖尿病 / メタボリックシンドローム / オートファジー / リソソーム

Outline of Final Research Achievements

In mammals, the inter-organ communications, in which the brain integrates informations from organs and transmits new regulational signals to others, plays a key role in maintaining metabolic homeostasis. However, under nutrient overloads due to energy excess, deterioration of these systems contributes to the development of metabolic syndrome.
In this study, we focus on the autophagy-lysosome pathway, especially in the liver, considered to be important for metabolism of major three nutrients (Carbohydrates, Lipids, and Amino acids). In mice models, modulation of this pathway through adenoviral gene delivery and Cre-LoxP systems has identified a new mechanism for the regulation of hepatic gluconeogenesis. In human hepatocytes, the expression of enzyme for gluconeogenesis also has been affected. In the future, the additional works are needed to clarify the precise mechanism and develop molecular targets for application.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、栄養素代謝の最終段階とされるオートファジー・リソソーム経路、特に肝臓に着目し、これまでの研究基盤を背景に発展することで、肝臓のみならず脂肪組織・筋肉組織などへの新しい臓器連携機構を解明することに繋がる。
現段階の本研究成果において、肝臓の糖新生に関わる新規機序が存在することを示唆する結果が得られている。今後、その他臓器への効果を解明することで、糖尿病への新しい予防・治療に結びつく可能性を秘めており、学術的・社会的意義を内包していると言えよう。