The role of TLR9 in the development of insulin resistance

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: FUKUDA Daiju 徳島大学, 大学院医歯薬学研究部, 特任講師 (40637568)
• Co-Investigator(Kenkyū-buntansha): SATA Masataka 徳島大学, 大学院医歯薬学研究部, 教授 (80345214)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 炎症 / マクロファージ / インスリン抵抗性 / ＴＬＲ９

Outline of Final Research Achievements

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains obscure. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed higher plasma cfDNA levels. cfDNA released from degenerated adipocytes promoted MCP-1expression in wild-type macrophages, but not in TLR9-deficient macrophages. In fat-fed wild-type mice, genetic deletion of Tlr9 or administration of a specific TLR9 antagonist demonstrated reduced adipose tissue inflammation and better insulin sensitivity compared with the control mice. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

Free Research Field

循環器・代謝性疾患