Expression of Adipokines by Intermittent Hypoxia and Its Molecular Mechanism
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 |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Nara Medical University |
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 |
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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Report
(4 results)
Research Products
(33 results)
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[Journal Article] TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared with malignant mesothelioma2021
Author(s)
Itami H, Fujii T, Nakai T, Takeda M, Kishi Y, Taniguchi F, Terada C, Okada F, Nitta Y, Matsuoka M, Sasaki S, Sugimoto S, Uchiyama T, Morita K, Kasai T, Kawaguchi R, Ohbayashi C.
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Journal Title
Human Pathology
Volume: 111
Pages: 59-66
DOI
Related Report
Peer Reviewed
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[Journal Article] Evaluation of DNA and RNA quality from archival formalin-fixed paraffin-embedded tissue for next-generation sequencing - Retrospective study in Japanese single institution.2020
Author(s)
Fujii T, Uchiyama T, Matsuoka M, Myojin T, Sugimoto S, Nitta Y, Okabe F, Sugimoto A, Sekita-Hatakeyama Y, Morita K, Itami H, Hatakeyama K, Ohbayashi C.
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Journal Title
Pathol Int.
Volume: 70(9)
Issue: 9
Pages: 602-611
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells.2018
Author(s)
Shobatake, R., Takasawa, K., Ota, H., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Uchiyama, T., Makino, M., Sugie, K., Takasawa, S. and Ueno, S.
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Journal Title
Int. J. Biochem. Cell Biol.
Volume: 95
Pages: 100-107
DOI
Related Report
Peer Reviewed
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[Presentation] Up-regulation of RETN, TNFα, and CCL2 mRNAs in Adipocytes by Intermittent Hypoxia and Its MicroRNA-Mediated Mechanism.2019
Author(s)
Uchiyama, T., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Shobatake, R., Ota, H., Takeda, M., Ohbayashi, C., and Takasawa, S.
Organizer
79th American Diabetes Association Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Up-regulation of RETN, TNFα, and CCL2 mRNAs in adipocytes by intermittent hypoxia via down-regulation of miR-452.2019
Author(s)
Uchiyama, T., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramot-Tsuchida, S., Shobatake, R., Ota, H., Takeda, M., Ohbayashi, C., and Takasawa, S.
Organizer
The 55th EASD Meeting
Related Report
Int'l Joint Research
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[Presentation] Up-regulation of expressions of PYY, GLP-1, and NTS by intermittent hypoxia in enteroendocrine cells2019
Author(s)
Ryogo Shobatake, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Mai Makino, Sumiyo Sakuramoto-Tsuchida, Tomoko Uchiyama, Nobuyuki Takahashi, Satoshi Ueno, Kazuma Sugie1 and Shin Takasawa
Organizer
55th Annual Meeting of the European Association for the Study of Diabetes
Related Report
Int'l Joint Research
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[Presentation] Up-regulation of PYY, GLP-1, and NTS by Intermittent Hypoxia in Enteroendocrine Cells2019
Author(s)
Ryogo Shobatake, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Mai Makino, Sumiyo Sakuramoto-Tsuchida, Tomoko Uchiyama, Nobuyuki Takahashi, Satoshi Ueno, Kazuma Sugie and Shin Takasawa
Organizer
79th American Diabetes Association Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Intermittent Hypoxia Up-regulates PYY, GLP-1, and NTS by in Enteroendocrine Cells2019
Author(s)
Ryogo Shobatake, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Mai Makino, Sumiyo Sakuramoto-Tsuchida, Tomoko Uchiyama, Nobuyuki Takahashi, Satoshi Ueno, Kazuma Sugie and Shin Takasawa
Organizer
XXIV World Congress of Neurology
Related Report
Int'l Joint Research
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[Presentation] The involvement of exon 75 of ryanodine receptor on insulin biosynthesis in pancreatic β cells.2019
Author(s)
Makino, M., Itaya-Hironaka, A., Yamauchi, A., Sakuramoto-Tsuchida, S., Uchiyama, T., Shobatake, R., and Takasawa, S.
Organizer
World Diabetes Congress 2019
Related Report
Int'l Joint Research
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[Presentation] Up-regulation of diabetes-associated myokines by intermittent hypoxia in mammalian skeletal muscle cells.2019
Author(s)
Takasawa, S., Shobatake, R., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Uchiyama, T., Tsuchida, C., and Ota, H.
Organizer
World Diabetes Congress 2019
Related Report
Int'l Joint Research
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[Presentation] Intermittent hypoxia up-regulates peptide YY, glucagon-like peptide-1, and neurotensin mRNAs in human enteroendocrine Caco-2 cells.2018
Author(s)
Shobatake, R., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Uchiyama, T., Ota, H., Sugie, K., Ueno, S. and Takasawa, S.
Organizer
The 41st Annual Meeting of the Japan Neuroscience Society
Related Report
Int'l Joint Research
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