Analysis of lipid metabolism regulation through chronic inflammation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Nippon Medical School (2018); Tokyo Medical and Dental University (2016-2017)
• Principal Investigator: Hayakawa Sumio 日本医科大学, 医学部, 助教 (00368292)
• Research Collaborator: CHENG YINGLAN
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脂質代謝 / 炎症 / カスパーゼ

Outline of Final Research Achievements

Inflammatory responses play a central role, as the front line, in the host defense against injury and infection. Under healthy conditions, acute inflammation can be resolved by means of an active termination program. Chronic inflammation is considered a risk factor for the development of pathological conditions, but the precise mechanism of their association is currently unknown. Recent studies have identified a link between inflammatory signaling and lipid signaling. In this study, we hypothesize that TLR-4 signaling activates an SREBP-mediated process through the inflammatory caspase and leads to elevated cholesterol synthesis in macrophages. Our study would provide new insight into the molecular mechanism of crosstalk between chronic inflammation and lipid metabolism signaling and offer new opportunities for the development of drug targets that ameliorate chronic inflammation.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

生活スタイルの変化に伴い、 わが国では平均寿命が過去最高を更新している。日本人の平均寿命が戦後急速に伸びた理由として、感染症などの急性期疾患の減少があげられる。一方で、近年増加している死因として、がんや心疾患などが関連した「生活習慣病」が大きな問題となっている。実際、生活習慣病が関連する死因は、日本人の死因の約５０～６０％を占めている。さらなる問題点として生活習慣病は、直接的な死因のみならず、重症化や合併症、生活機能の低下・要介護など生活の質（QOL）の低下の原因ともなる。すなわち、慢性炎症が関わる生活習慣病の予防や治療につながるメカニズムを解明することは、健康寿命を延伸するために急務である。