Elucidation of the function of novel transcription factor that lead to polarization of M2 macrophages and development of metabolic disease drug discovery

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K11764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kanazawa University
• Principal Investigator: Nagashimada Mayumi 金沢大学, 保健学系, 助教 (30645510)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肥満 / 慢性炎症 / インスリン抵抗性 / マクロファージ / 転写因子

Outline of Final Research Achievements

Recently, it has been known that not only macrophage infiltration but also macrophage polarization (M1: pro-inflammatory, M2: anti-inflammatory) is important in the obesity-associated inflammation and insulin resistance. However, the regulatory mechanism of macrophage polarization in obesity is unknown. We found that the heat shock factor HSF1 was reduced in obese adipose tissue. In this study, we examined at the role of HSF1 expressed on macrophages in the regulation of macrophage polarization, obesity-associated chronic inflammation and metabolic diseases. We have discovered that HSF1 expression in macrophages has been shown to be involved in the macrophages infiltrating obese adipose tissue and macrophages polarization and plays a crucial role in glucose and lipid metabolism, insulin resistance, and inflammation in obesity.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、転写因子であるHSF1がマクロファージの極性制御および肥満による慢性炎症やインスリン抵抗性の発症に関与することを明らかにし、HSF1が生活習慣病の元凶となる肥満と慢性炎症のリンクを断ち切る因子となりうる可能性を示した研究である。肥満による慢性炎症とインスリン抵抗性の発症に重要なマクロファージの極性という「質」を変化させるHSF1はインスリン抵抗性や生活習慣病に対する創薬、予防法につながる新規標的分子となりうることが期待される。