the metabolic changes in macrophages that promote obesity-associated liver cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16143
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: University of Toyama
• 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)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: マクロファージ / 肝がん / HIF-1α

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.

Free Research Field

代謝

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。