| Project/Area Number |
22K20890
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Yokohama City University |
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Principal Investigator |
SUZUKI Toru 横浜市立大学, 附属病院, 指導診療医 (40963442)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ATRAP / 脂肪細胞 / 免疫細胞 / マクロファージ / 代謝障害 / 内臓脂肪型肥満 / 肥満症 / M2マクロファージ / TGF-β / 心腎連関症候群 / レニン-アンジオテンシン / 心腎連関 / レニンアンジオテンシン系 |
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| Outline of Research at the Start |
心腎連関モデル動物，ATRAP遺伝子改変動物およびヒト白血球検体などを用いて，心腎連関症候群におけるマクロファージのATRAPの病態生理学的意義を解明し，ATRAPに着目した新規分子標的治療法の開発に向けた検討を行う．
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| Outline of Final Research Achievements |
We conducted bone marrow transplantation to generate two types of chimeric mice: bone marrow wild-type chimeric (BM-WT) and bone marrow ATRAP knockout chimeric (BM-KO) mice. These chimeric mice were provided an high-fat diet (HFD) to induce visceral obesity. BM-KO mice had significantly reduced obesity induced by HFD compared to BM-WT mice. In addition, BM-KO mice on the HFD showed significant improvements in white adipose tissue metabolism, inflammation, glucose
tolerance, and insulin resistance, compared with BM-WT mice on the HFD. Detailed analysis of white adipose tissue revealed significant suppression of HFD-induced activation of transforming growth factor-beta signaling via amelioration of CD206+ (M2) macrophage accumulation in the adipose tissue of BM-KO mice. Finally, transcriptome analysis of monocytes indicated the possibility of genetic changes, such as the enhancement of interferon-γ response at the monocyte level, affecting macrophage differentiation in BM-KO mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果は、内臓脂肪型肥満の発症・進展に免疫細胞ATRAPが重要な役割を果たしていることを明らかとした。また、骨髄・免疫細胞中のATRAPの発現は、内臓脂肪型肥満のバイオマーカーやサロゲートマーカーとして応用できる可能性が期待される。さらに、免疫細胞ATRAPの発現制御は内臓脂肪型肥満の新たな治療標的となる可能性もあり、将来的には新規の肥満症治療の開発につながることも期待される。
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