The role of lipid metabolism alteration in asthma: Mechanism and clinical implication

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08197
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: Morishima Yuko 筑波大学, 医学医療系, 准教授 (10375511)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 喘息 / アレルギー性気道炎症 / 脂肪酸 / 長鎖脂肪酸伸長酵素 / Elovl6

Outline of Final Research Achievements

In the present study, we found that ELOVL6 expression was downregulated in the bronchial epithelium of patients with severe asthma compared with controls. We then investigated the contribution of ELOVL6 to allergic airway inflammation using Elovl6-deficient mice exposed to OVA. In asthmatic mice, ELOVL6 deficiency led to enhanced airway inflammation in which lymphocyte egress from lymph nodes was increased, and both type 2 and non-type 2 immune responses were upregulated. Lipidomic profiling revealed that the levels of palmitic acid, ceramides, and sphingosine 1-phosphate were higher in the lungs of Elovl6-deficient asthmatic mice compared with those of wild-type mice, while the aggravated airway inflammation was ameliorated by treatment with fumonisin B1 or DL-threo-dihydrosphingosine, inhibitors of ceramide synthase and sphingosine kinase, respectively.

Free Research Field

アレルギー性呼吸器疾患の病態生理

Academic Significance and Societal Importance of the Research Achievements

脂質代謝異常が喘息の病態成立に与える影響について、分子細胞生物学的な側面からアプローチした研究はきわめて少ない。これまでに行われた研究の多くは組織に蓄積する脂質の「量」に着目し、とくに生体内で合成されないω3やω6必須脂肪酸を中心に、それらの「摂取量」によってアレルギー性気道炎症が修飾されることが報告されている。これに対して本研究は、生体内で合成される脂肪酸を含めた包括的な脂質の不均衡が喘息の増悪をもたらす病態について明らかにするものであり、その成果は新たな治療の確立に寄与するものと考えている。