The identification of undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H03252
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Tohoku University
• Principal Investigator: Sugawara Akira 東北大学, 医学系研究科, 教授 (90270834)
• Research Collaborator: YOKOYAMA atushi ; KUDO masataka ; DOI takayuki ; ITO ryo ; SHIMADA hiroki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アルドステロン / 肥満 / 高血圧 / 脂肪細胞 / CYP11B2

Outline of Final Research Achievements

Obese patients are well known to be highly complicated with hypertension. Recently, “undetermined” adipocyte-derived factor(s) have been recognized as one of the causes of the obesity-related hypertension independent of angiotensin II. In the present study, we aim to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression and aldosterone secretion that may induce hypertension. We first differentiated mouse fibroblast 3T3-L1 cells into adipocytes, and collected their supernatants. The supernatants were then incubated with human adrenocortical carcinoma H295R cells, and their ability to stimulate CYP11B2 mRNA expression was indicated. Thereafter, the supernatants were fractionated by ultrafiltration to obtain active fractions that stimulate CYP11B2 expression, and proteins included in the fractions were analyzed by LC-MS/MS. We finally obtained factor "X" which was demonstrated to stimulate CYP11B2 expression significantly.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

肥満患者における高血圧の制御は、国民の健康寿命延伸・医療費削減の両面から喫緊の課題である。本研究課題の遂行により新規昇圧因子"X"が得られたが、今後は本因子を基盤とした肥満高血圧の新規診断・治療法の開発を進める。これらの遂行により、肥満高血圧に起因する心血管イベントの発症を二次的に抑制することが可能となり、患者さんへの福音となるとともに、本邦の医療費抑制にも大きく貢献することが期待される。