Adipose (pro)renin receptor and multiple organ damage in metabolic syndrome

• Project/Area Number: 18K16212
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Seki Yasufumi 東京女子医科大学, 医学部, 助教 (20649488)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 肥満 / レニン-アンジオテンシン系 / プロレニン / 炎症 / 成長ホルモン / 低酸素 / メタボリック症候群 / 脂肪組織 / （プロ）レニン受容体

Outline of Final Research Achievements

We investigated the role of adipose (pro)renin receptor [(P)RR] on tissue renin-angiotensin system and fat disposition in growth hormone deficiency, which cause visceral obesity. Serum (P)RR level was increased in obese mice and growth hormone deficiency by growth hormone receptor antagonist increased adipose (P)RR expression. In addition, (P)RR expression in subcutaneous fat was also increased in GH-deficient patients and significantly correlated with IGF-1 SD score. Adipose (P)RR expression might be increased in GH deficiency and contribute to activation of tissue renin-angiotensin system.

Academic Significance and Societal Importance of the Research Achievements

欧米型食生活や運動不足は内臓脂肪の蓄積を介してメタボリック症候群を引き起こし、高血圧、糖尿病、脂質異常症を介して死亡率上昇やQOL低下につながる。成長ホルモン分泌不全症は内臓脂肪蓄積型肥満を引き起こし、重篤な合併症を呈する。本研究成果から脂肪組織(P)RRを介したメタボリック症候群における新たな臓器障害の機序の解明に応用できる可能性がある。

Research Products

• [Journal Article] Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors (2022)
  • Author(s): Seki Yasufumi、Ichihara Atsuhiro
  • Journal Title: PLOS ONE Volume: 17 Issue: 4 Pages: e0267324-e0267324
  • DOI: 10.1371/journal.pone.0267324
  • Peer Reviewed
• [Presentation] 非機能性下垂体腫瘍患者における成長ホルモン分泌不全と高感度CRPの関連 (2022)
  • Author(s): 関康史、高野倫嘉、山下薫、木田可奈子、佐々木信和、石川透、木村美和、渡邊智、堀内咲由莉、伊上優子、佐野央、平田清貴、小宅健太郎、北山さおり、渡辺大輔、森本聡、市原淳弘
  • Organizer: 第32回日本間脳下垂体腫瘍学会
• [Presentation] 非機能性下垂体腫瘍患者におけるGH分泌不全と高感度CRPとの関連 (2021)
  • Author(s): 関康史、市原淳弘
  • Organizer: 第31回日本間脳下垂体腫瘍学会
• [Presentation] Increased Serum High-sensitivity C-reactive Protein in Growth Hormone-deficient Patients with Non-functioning Pituitary Tumors (2021)
  • Author(s): Yasufumi Seki, Atsuhiro Ichihara
  • Organizer: The Endocrine Society's 103rd Annual Meeting and Expo
• [Presentation] 非機能性下垂体腫瘍に合併する成人GH分泌不全と高感度CRPの関連 (2021)
  • Author(s): 関康史、市原淳弘
  • Organizer: 第94回日本内分泌学会総会