| Project/Area Number |
18K15067
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
Uchiyama Tomoko 奈良県立医科大学, 医学部附属病院, 研究員 (80745448)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | sleep apnea syndrome / intermittent hypoxia / adipokine / insuline resistance / micro RNA / microRNA / アディポカイン / 間歇的低酸素 |
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| Outline of Final Research Achievements |
IH (intermittent hypoxia) is considered to cause adipose tissue inflammation, leading to insulin resistance. In this study, we exposed mouse 3T3-L1 and human SW872 adipocytes to experimental IH or normoxia, and analyzed mRNA expression of several adipokines. We found that the mRNA levels of RETN, TNFα and CCL2 in SW872 cells and 3T3-L1 adipocytes were significantly increased by IH. RETN, TNFα, and CCL2 in IH-treated cell medium were also increased. The promoter activities of these genes were not increased by IH. Target mRNA search of microRNA (miR)s revealed that all the mRNAs have a potential target sequence for miR-452. The miR-452 level of IH-treated cells was significantly decreased. These results indicate that IH stress down-regulates the miR-452 in adipocytes, resulting in the increased levels of RETN, TNFα, and CCL2 mRNA, leading SAS patients to insulin resistance.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は睡眠時無呼吸症候群患者が曝露される間歇的低酸素とインスリン抵抗性の関連に着目したものであり、関与する諸臓器のうち、脂肪細胞から分泌されるアディポカインの発現量の変化及び発現調節機序を解明しようとしたものである。IH曝露が脂肪細胞のアディポカイン分泌に影響を与え、インスリン抵抗性を増悪させる可能性が示唆されたため、今後、SAS患者を対象として、アディポカインをターゲットとした糖尿病予防・治療につながる研究に発展させられる可能性がある。また、アディポカイン発現調節機構には、microRNAの関与が考えられたため、これについても治療ターゲットとなる可能性を示す事が出来た。
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