Visualization of chronic inflammation in arterial wall and perivascular adipose tissue

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293184
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SATA Masataka 徳島大学, 大学院医歯薬学研究部, 教授 (80345214)
• Co-Investigator(Kenkyū-buntansha): HORIKAWA Kazuki 徳島大学, 大学院医歯薬学研究部, 教授 (70420247) ; FUKUDA Daiju 徳島大学, 大学院医歯薬学研究部, 特任講師 (40637568) ; HIGASHIKUNI Yasutomi 東京大学, 医学部附属病院, 助教 (10586481)
• Co-Investigator(Renkei-kenkyūsha): SATOMI Junichi 徳島大学, 大学院医歯薬学研究部, 准教授 (10304510) ; NAKAYAMA Taisuke 徳島大学, 病院, 医員 (80582791)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 動脈硬化 / 慢性炎症 / メタボリックシンドローム / インスリン抵抗性 / 肥満 / 自然免疫

Outline of Final Research Achievements

Chronic inflammation closely associates with insulin resistance. TLR9 recognizes bacterial unmethylated DNA, although it can also provoke inflammation in response to fragmented DNA from mammalian cells. The role of TLR9 in the development of insulin resistance, however, remains unknown. This study tested the hypothesis that TLR9 signal promotes inflammation in metabolic organs and causes insulin resistance in high-fat fed mice. GTT and ITT demonstrated that disruption of TLR9 improved insulin resistance . TLR9 KO mice had less macrophage infiltration and MCP-1 expression in fat tissue. In vitro experiments showed that CpG ODN, synthetic oligonucleotides that contain unmethylated CpG, can promote the expression of pro-inflammatory molecules in WT macrophages, but not in TLR9 KO macrophages. Our results suggested that genetic ablation of TLR9 improved insulin resistance through the inhibition of inflammatory responses in fat tissue caused by accumulation and activation of macrophages.

Free Research Field

循環器内科学