Elucidating a potential mechanistic link between altering lipid metabolism on the alveolar type II epithelial cells and pathogenesis of pulmonary fibrosis and pulmonary emphysema

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19442
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: SUNAGA HIROAKI 群馬大学, 大学院医学系研究科, 研究員 (10760077)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脂肪酸組成 / リン脂質 / 肺線維症 / 肺気腫 / 飽和脂肪酸 / 不飽和脂肪酸 / 肺胞上皮細胞 / 喫煙

Outline of Final Research Achievements

Despite the established role of alveolar type II epithelial cells for the maintenance of pulmonary function and synthesis of pulmonary surfactant, little is known about the deregulation of lipid metabolism in the pathogenesis of pulmonary fibrosis and pulmonary emphysema. We have focused on the elongase of long chain fatty acids family 6 (Elovl6) which is a catalytic enzyme that elongates of saturated and monounsaturated long chain fatty acids in the lung. We used pulmonary fibrosis and pulmonary emphysema model of wild type (WT) mice and Elovl6-null (Elovl6-/-) mice. Interestingly, Elovl6-mediated derangement of fatty acid composition lead to change of apoptosis and differentiation, and alteration of expression of phospholipid synthetase such as LPCAT1 and LPCAT4, resulting in progression of lung disease. Our findings suggest that regulation of lipid metabolism by Elovl6 would become a new therapeutic target for pulmonary fibrosis and pulmonary emphysema.

Free Research Field

脂質代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究結果により、Ⅱ型肺胞上皮細胞における脂質代謝の変化が肺線維症および肺気腫の病態形成に関与することが見い出せた。また、食事中の脂肪酸の組成やバランス、糖尿病などの疾患に伴う体内の脂肪酸組成の変化が病態の発症および進展に関わる可能性が示唆された。Elovl6酵素の発現や活性変化に伴う脂肪酸組成の変化が病態形成に重要であることから、今後は、生活習慣と肺疾患発症との因果関係の解明や、Elovl6の発現や活性を制御する食事成分、薬剤の解明などを行うことで肺疾患予防・治療への効果が期待でき、その波及効果は大きいと考えられる。