Control of obesity and energy metabolism by regulator of bone metabolism, and its physiological and pathological role.
| Project/Area Number |
17K11041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Hino Jun 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40260351)
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| Co-Investigator(Kenkyū-buntansha) |
宮里 幹也 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (50291183)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 肥満・糖尿病 / CNP / 血管内皮細胞 / 脂肪細胞 / エネルギー代謝 / 骨代謝 / 臓器連関 / BMP / 肥満 / 臓器関連 / ペプチド / 抗炎症 / BMP-3b / NASHインスリン抵抗性 / 炎症 / 線維化 / 代謝 / 糖尿病 / インスリン抵抗性 / 血管内彼細胞 / 骨代謝調節 |
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| Outline of Final Research Achievements |
Recently, we have reported that bone morphogenetic protein-3b（BMP-3b）acts as regulator of both bone metabolism and obesity/energy metabolism. While, C-type natriuretic peptide (CNP) is present in bone tissues and one of the regulators of bone metabolism (bone elongation factor). Considering the characters of BMP-3b and CNP, we predicted that CNP might be regulator of obesity/obesity and energy metabolism. In this research, we showed that CNP also possessed beneficial effects against obesity/diabetes accompanying increased energy expenditure using two types of CNP transgenic mice (A-CNP and E-CNP). A-CNP is a transgenic mice (Tg) that overexpress CNP in adipocytes, and E-CNP is a Tg that overexpress CNP in endothelial cells. These results indicated that both regulators for bone metabolism also have common beneficial effects in obesity/diabetes, which enable to clarify and demonstrate the role and mechanism of inter-organ communication based on bone tissues.
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| Academic Significance and Societal Importance of the Research Achievements |
CNPの肥満・エネルギー代謝調節については不明であり、さらに、脂肪組織や血管由来のCNPに着目したこれら作用についても新たな知見となる。CNPとBMP-3bは、共に骨代謝調節因子としての役割が知られているが、骨代謝のみならず肥満・エネルギー代謝においても、両者の関連性や相互作用についての報告はなく、本研究の学術的な大きな特色の一つである。更に、本成果を基盤とした臨床応用研究により、肥満病態解明、治療薬開発へも繋がる。実際、ヒトの肥満では、CNPやBMP-3bの発現量変動も報告されていることから、その実現性は高く、社会的意義は大きい。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Deficiency of natriuretic peptide signaling promotes peripartum cardiomyopathy-like remodeling in the mouse heart.2020
Author(s)
Otani K, Tokudome T, Kamiya CA, Mao Y, Nishimura H, Hasegawa T, Arai Y, Kaneko M, Shioi G, Ishida J, Fukamizu A, Osaki T, Nagai-Okatani C, Minamino N, Ensho T, Hino J, Murata S, Takegami M, Nishimura K, Kishimoto I, Miyazato M, Harada-Shiba M, Yoshimatsu J, Nakao K, Ikeda T, Kangawa K.
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Journal Title
Circulation
Volume: 141
Issue: 7
Pages: 571-588
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Overexpression of C-type Natriuretic Peptide in Endothelial Cells Protects against Insulin Resistance and Inflammation during Diet-induced Obesity.2017
Author(s)
Bae CR, Hino J, Hosoda H, Arai Y, Son C, Makino H, Tokudome T, Tomita T, Kimura T, Nojiri T, Hosoda K, Miyazato M, Kangawa K.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 9807-9807
DOI
Related Report
Peer Reviewed / Open Access
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