The exploration of pathophysiology of chronic stress and its therapeutic targets
| Project/Area Number |
16K15411
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Saitama Medical University (2018-2019)
Nagoya University (2016-2017) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ストレス / 情動ストレス / ACE2 / レニン-アンギオテンシン系 / キサンチン酸化酵素 / DPP－４ / 慢性炎症 / 酸化ストレス / 耐糖能異常 / Dipeptidyl Peptidase-4 / 内科 |
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| Outline of Final Research Achievements |
Chronic stress is closely linked to the metabolic syndrome, diabetes, hyperuricemia and thromboembolism, but the mechanisms remain elusive. We reported that stress targets visceral adipose tissue (VAT), inducing lipolysis, low-grade inflammation with production of inflammatory adipokines, metabolic derangements such as insulin resistance, and prothrombotic state. We recently showed that DPP-4 and xanthine oxidoreductase (XOR) are involved in the VAT inflammation.
Furthermore, two-week daily restraint stress activated the classical renin-angiotensin system (RAS) to evoke intestinal inflammation in mice, and perturbate microbiota and serotonin metabolism.
The treatments with DPP-4 inhibitor, XOR inhibitor, and angiotensin II receptor blocker respectively improved the stress-induced pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性ストレスはメタボリック症候群、糖尿病、高尿酸血症、血栓症の原因となりうるが、機序は不明であったが、これを明らかにした。特に高血圧、糖尿病、高尿酸血症治療薬でこれらの病態を抑えることができたのはdrug repositioning、成人病、メタボリック症候群の治療の動機付けになると考える。
これらの結果についてプレスリリースを行ったところ、マスコミ各社より取材、SNSで話題になるなど社会的な関心の高さがうかがえた。
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Report
(5 results)
Research Products
(7 results)
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[Journal Article] Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy.2017
Author(s)
Fukaya K, Takeshita K, Okumura T, Hiraiwa H, Aoki S, Ichii T, Sugiura Y, Kitagawa K, Kondo T, Watanabe N, Kano N, Furusawa K, Sawamura A, Morimoto R, Bando Y, Murohara T.
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Journal Title
Ann Noninvasive Electrocardiol.
Volume: 22
Issue: 5
DOI
Related Report
Peer Reviewed
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