| Project/Area Number |
17K16143
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | University of Toyama |
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Principal Investigator |
Takikawa Akiko 富山大学, 大学院医学薬学研究部(医学), 客員助教 (80647454)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | マクロファージ / 肝がん / HIF-1α / 肥満 / 癌 |
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| Outline of Final Research Achievements |
We have recently reported that HIF-1α in liver macrophages (mφ) is activated, which promote liver cancer in obese mice. In this study, I examined the mechanisms for the activation of mφ HIF-1α during obesity. The incidence of liver cancer in obesity and chemical carcinogen-induced liver cancer model mice was reduced by mφ-specific HIF-1α-deficiency by about 45%. Reduction in liver inflammation and ERK activation was considered to contribute to the reduced incidence of liver cancer.
Since HIF-1α of liver mφ in obese mice was activated in hypoxia-independent manner, intracellular metabolites of liver mφ was analyzed. However, succinate and other metabolites, which had been speculated to activate HIF-1α, did not change between obese and lean mice. Further studies are needed to identify the factors activating the HIF-1α in liver mφ during obesity in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満時に肝臓マクロファージ（mφ）のHIF-1αが活性化し、肝がん発症を促進することを学術論文で報告した。また肥満時の肝がん発症の機序として肝臓での炎症反応およびERK活性化が関与することを明らかにした。
mφ内でHIF-1αを活性化する代謝物の同定には至らず、肝臓マクロファージの抽出、メタボローム解析の手法の見直し、変更が必要であると考えられた。mφHIF-1αを活性化する因子の同定は今後の課題である。
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