2019 Fiscal Year Final Research Report
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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| Keywords | ストレス |
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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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| Free Research Field |
内科学一般(含心身医学)
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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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