Targeting Cellular Metabolism for the Treatment of Lifestyle-related Disease

• Project/Area Number: 17H04172
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Niigata University
• Principal Investigator: Tohru Minamino 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 細胞老化 / 細胞内代謝

Outline of Final Research Achievements

Activation of brown/beige adipose tissue has been suggested as a therapeutic strategy for metabolic disorders. While activation of brown/beige adipose tissue is associated with mobilization of both glucose and lipids, few studies have focused on the role of glycolytic enzymes in regulating adipose tissue function. We generated mouse models with specific deletion of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) from adipose tissue. Our results suggest a cell-autonomous mechanism, in which inhibition of glycolysis leads to beiging of visceral WAT secondary to downregulation of autophagy by mTor. Targeting this mechanism is potentially a novel therapeutic strategy for obesity and diabetes.

Academic Significance and Societal Importance of the Research Achievements

「細胞内代謝不全を標的とした生活習慣病の診断・治療法開発」についての研究は、きわめて新規で独創性の高い課題である。また、その成果として、代謝産物を標的とした新規の降圧薬・心不全治療薬・代謝治療薬の開発などが十分に期待できる。