New approch for for wasting SAT with COPD to overcome cachexia and comorbidities

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09556
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: TSUJI TAKAO 東京医科大学, 医学部, 講師 (30459664)
• Co-Investigator(Kenkyū-buntansha): 青柴 和徹 東京医科大学, 医学部, 教授 (60231776)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: COPD / 肺気腫 / やせ / 皮下脂肪 / EP3

Outline of Final Research Achievements

Chronic obstructive pulmonary disease (COPD) is often associated with cachexia including wasting subcutaneous adipose tissue (SAT) and comorbidities that have a significant impact on its prognosis. Since SAT plays an important role in energy homeostasis, the lower capacity for storage of surplus energy in wasting SAT with COPD may cause ectopic fat accumulation in the visceral adipose tissue, which could then lead to metabolic syndrome. We explored the new approach for wasting SAT with COPD to overcome cachexia and comorbidities. We identified increased EP3 expression in wasting SAT in a mouse model of pulmonary emphysema and patients with COPD. Targeting the EP3 expression in wasting SAT with COPD may be developed as a useful therapeutic intervention in cachexic emphysema patients.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、COPD患者の予後規定因子である体重減少とCOPD併存症に対する新しい治療法の開発を、皮下脂肪の役割に着眼し行った。COPD特に気腫型COPDではエネルギー貯蔵の場としての皮下脂肪の減少が著明であるが、皮下脂肪量の改善はエネルギー貯蓄機能改善から併存症改善につながりうる。マウスモデルの検討で、減少する皮下脂肪ではEP3発現が亢進し、COPD症例の皮下脂肪でEP3発現が増加していた。よって、皮下脂肪組織内のEP3発現に介入しうる創薬は、COPD皮下脂肪の改善から併存症の創薬につながると期待される。