Identification of a novel adipocyte-derived factor that elevates blood pressure using VIKING method

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22793
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Tohoku University
• Principal Investigator: Sugawara Akira 東北大学, 医学系研究科, 教授 (90270834)
• Co-Investigator(Kenkyū-buntansha): 横山 敦 東北大学, 医学系研究科, 助教 (20572332)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: アルドステロン合成酵素 / 脂肪細胞 / メタボリック症候群 / 治療抵抗性高血圧 / 新規創薬

Outline of Final Research Achievements

Hypertension is a frequently observed complication among obese patients with metabolic syndrome. In this study, we aim to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression and aldosterone secretion that may induce obesity-related hypertension. We first differentiated mouse fibroblast 3T3-L1 cells into adipocytes, and collected their supernatants. The supernatants were incubated with human adrenocortical carcinoma H295R cells, and their CYP11B2 mRNA expression was measured by quantitative PCR with reverse transcription. The supernatants were then purified by anion-exchange chromatography and were further fractionated by LC-MS/MS. We then identified several candidate proteins and are investigating their function by shRNA.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行により、脂肪細胞由来の未知の液性昇圧因子の本態が初めて明らかとなるとともに新規創薬のターゲットが明確化されることから、本邦で2,700万人と推定されるメタボリック症候群・予備軍患者中に数多く存在する肥満高血圧患者の診断・治療に大きな福音をもたらす事が可能となる。特に、肥満高血圧患者において顕著な治療抵抗性高血圧に対しては、新規創薬・治療法の開発に向けて大きく貢献できると期待される。