A study of the relationships between glucocorticoids action in the skeletal muscle and the regulation of the body composition and energy metabolism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08973
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yoshikawa Noritada 東京大学, 医科学研究所, 特任准教授 (70396878)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: グルココルチコイド / グルココルチコイド受容体 / 骨格筋代謝 / エネルギー代謝 / 多臓器連関 / 性差 / 加齢

Outline of Final Research Achievements

In this study, skeletal muscle-specific glucocorticoid receptor-knockout mice (GRmKO), which cause spatial changes in energy storage such as skeletal muscle hypertrophy and fat atrophy, were bred under various conditions and studied by multi-omics approaches. The purpose of this study is to clarify the mechanism of such whole-body energy metabolism, especially its relationship with glucocorticoid action in the skeletal muscle. While differences in metabolic networks were observed between wild-type and GRmKO mice, it was shown that there may be a metabolic network that is firmly maintained regardless of energy storage changes (changes in body composition). It has also been shown that these metabolic networks and their key molecules may be affected by aging and sex.

Free Research Field

内分泌代謝

Academic Significance and Societal Importance of the Research Achievements

本研究は、骨格筋グルココルチコイド作用に着目して、エネルギーフローの揺らぎを有するモデル動物と数理科学的手法を駆使してその解明を目指すものであり、エネルギー代謝システム・代謝可塑性の包括的理解、肥満や糖尿病、サルコペニア(加齢性筋萎縮)などの代謝関連疾患の合理的な予測・予防法および治療戦略の創成基盤の構築につながる。また、性差や生命予後のバイオマーカーとなる因子の発見も期待される。個人のゲノム情報などとの結合によって代謝疾患の合理的な個別化医療の確立に繋がる可能性も大である。