Transomics analysis of glucose-responsive metabolic regulation through crosstalk between the liver and muscle and its alterations associated with obesity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16349
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Kokaji Toshiya 奈良先端科学技術大学院大学, データ駆動型サイエンス創造センター, 助教 (80822551)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: トランスオミクス / 臓器連関 / 肥満 / インスリン / マルチオミクス

Outline of Final Research Achievements

To understand the mechanism of dysfunction of the inter-organ metabolic cycle in obesity, we constructed metabolic regulatory networks of liver and muscle, which are major glucose metabolizing organs, in wild-type mice and obesity model mice, and integrated them to construct a transomic network that crosses the liver and muscle.
As a result, we newly constructed a muscle glucose responsive transomic network, which can be compared and integrated with the liver network. We found that metabolites themselves do not regulate metabolism in the muscle of obese mice, but are instead regulated by gene expression.

Free Research Field

オミクス解析

Academic Significance and Societal Importance of the Research Achievements

肥満により肝臓や筋肉に脂肪が蓄積すると、糖や脂質の代謝制御がうまくいかず、血液中のグルコース濃度や脂質濃度が異常に高まり、動脈硬化など様々な疾患の原因となります。本研究では、グルコース投与という摂食に近い条件での筋肉における代謝制御ネットワークを初めて大規模に明らかにし、肝臓ネットワークとの統合により血糖及び血中脂質の恒常性の破綻メカニズムの全容が明らかとなることが期待されます。