Elucidation of the mechanism of the innate immune signal that induces hypothalamic inflammation and feeding dysfunction
Project/Area Number |
15K08527
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
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Research Institution | University of Toyama |
Principal Investigator |
NAGAI Yoshinori 富山大学, 大学院医学薬学研究部(医学), 客員教授 (30431761)
|
Co-Investigator(Renkei-kenkyūsha) |
WATANABE Yasuharu 富山大学, 大学院医学薬学研究部(医学), 客員准教授 (80646307)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 自然免疫 / 視床下部炎症 / 摂食異常 / レプチン抵抗性 |
Outline of Final Research Achievements |
We found that a TLR signaling molecule TRIF had an important role in the pathogenesis of high-fat diet (HFD)-induced hypothalamic inflammation and leptin resistance. We demonstrated that TRIF was expressed in the hypothalamus of wild-type mice by in situ hybridization. In vivo analyses revealed that HFD- or an intrinsic TLR3 ligand Stathmin-induced inflammation and reduced leptin signaling in the hypothalamus were improved in TRIF-deficent mice compared with wild-type mice. However, TLR3-deficent mice showed different phenotypes from TRIF-deficent mice, suggesting that another molecule other than TLR3 may be responsible for TRIF-induced hypothalamic inflammation and leptin resistance.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.2017
Author(s)
S. Yamamoto, M. Muramatsu, E. Azuma, M. Ikutani, Y. Nagai, H. Sagara, B.N. Koo, S. Kita, E. O’Donnell, T. Osawa, H. Takahashi, K.I. Takano, M. Dohmoto, M. Sugimori, I. Usui, Y. Watanabe, N. Hatakeyama, T. Iwamoto, I. Komuro, K. Takatsu, K. Tobe, S. Niida, N. Matsuda, M. Shibuya, M. Sasahara
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Journal Title
Sci Rep
Volume: 7:3855
Issue: 1
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex2017
Author(s)
Okamoto N, Mizote K, Honda H, Saeki A, Watanabe Y, Yamaguchi-Miyamoto T, Fukui R, Tanimura N, Motoi Y, Akashi-Takamura S, Kato T, Fujishita S, Kimura T, Ohto U, Shimizu T, Hirokawa T, Miyake K, Fukase K, Fujimoto Y, Nagai Y, Takatsu K
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Journal Title
Journal of Biological Chemistry
Volume: 292
Issue: 37
Pages: 15378-15394
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance2017
Author(s)
Wada T, Ishikawa A, Watanabe E, Nakamura Y, Aruga Y, Hasegawa H, Onogi Y, Honda H, Nagai Y, Takatsu K, Ishii Y, Sasahara M, Koya D, Tsuneki H, Sasaoka T
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Journal Title
J Endocrinol.
Volume: 235
Issue: 3
Pages: 179-191
DOI
Related Report
Peer Reviewed
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[Journal Article] Inflammatory responses increase secretion of MD-1 protein2016
Author(s)
Thomas Jennings R, Odkhuu E, Nakashima A, Morita N, Kobayashi T, Yamai I, Tanaka M, Suganami T, Haga S, Ozaki M, Watanabe Y, Nagai Y, Takatsu K, Kikuchi-Ueda T, Ichimonji I, Ogawa Y, Takagi H, Yamazaki T, Miyake K, Akashi-Takamura S
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Journal Title
International Immunology
Volume: 28
Issue: 10
Pages: 503-512
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance.2016
Author(s)
Takikawa A, Mahmood A, Nawaz A, Kado T, Okabe K, Yamamoto S, Arif A, Senda S, Tsuneyama K, Ikutani M, Watanabe Y, Igarashi Y, Nagai Y, Takatsu K, Koizumi K, Imura J, Goda N, Sasahara M, Matsumoto M, Saeki K, Nakagawa T, Fujisaka S, Usui I, Tobe K.
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Journal Title
Diabetes
Volume: 65(12)
Issue: 12
Pages: 3649-3659
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Deletion of SIRT1 in myeloid cells impairs glucose metabolism with enhancing inflammatory response to adipose tissue hypoxia2016
Author(s)
Akiko Takikawa, Isao Usui , Shiho Fujisaka, Masashi Ikutani, Satoko Senda, Shinpei Hattori, Koichi Tsuneyama, Yukiko Koshimizu, Ran Inoue, Ayumi Tanaka-Hayashi, Takashi Nakagawa, Yoshinori Nagai, Kiyoshi Takatsu, Toshiyasu Sasaoka, Hisashi Mori, Kazuyuki Tobe
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Journal Title
Diabetology International
Volume: 7
Issue: 1
Pages: 59-68
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice.2016
Author(s)
Watanabe Y, Nagai Y, Honda H, Okamoto N, Yamamoto S, Hamashima T, Ishii Y, Tanaka M, Suganami T, Sasahara M, Miyake, K, Takatsu K.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 23097-23097
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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