2021 Fiscal Year Final Research Report
Deficiency of indoleamine 2,3-dioxygenase 2 is associated with the development of lifestyle-related diseases.
| Project/Area Number |
19K07490
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Yamamoto Yasuko 藤田医科大学, 保健学研究科, 准教授 (00331869)
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| Co-Investigator(Kenkyū-buntansha) |
藤垣 英嗣 藤田医科大学, 保健学研究科, 講師 (00612631)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | トリプトファン代謝酵素 / 生活習慣病 / インシュリン抵抗性 |
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| Outline of Final Research Achievements |
Indoleamine 2,3-dioxygenase 2(IDO2), an isoform of IDO1, is a rate-limiting enzyme that catalyzes the initial reaction of the tryptophan kynurenine pathway, a major pathway in the metabolism of tryptophan. In this study, IDO2 knockout mice were fed a high-fat diet to investigate the effects of IDO2 deficiency on the inflammatory response of adipocytes and its involvement in the pathogenesis of lifestyle-related diseases.
In IDO2 knockout mice at 4 weeks after administration of a high-fat diet, significant increases were observed in serum biochemical parameters, namely, fasting blood glucose, cholesterol, and alanine aminotransferase. Furthermore, a blood glucose tolerance test showed increased insulin resistance in IDO2 knockout mice.In the long-term high-fat diet group, increased liver fibrosis was observed in IDO2 knockout mice compared with wild-type mice. Our results suggest that the deficiency of IDO2 might be a risk factor for lifestyle-related diseases.
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| Free Research Field |
病態生化学
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| Academic Significance and Societal Importance of the Research Achievements |
生活習慣病は、不健全な生活の積み重ねによる内臓脂肪型肥満が原因となり引き起こされる。わが国においても生活習慣の変化による肥満率の増加は生活習慣病の増加につながる深刻な課題である。
本検討によりトリプトファン代謝酵素であるIDO2の欠失は、高脂肪食負荷により肝臓への脂肪蓄積およびインシュリン抵抗性を亢進する事が明らかとなった。さらに長期の高脂肪食負荷は、肝臓の線維化の亢進を認めた。IDO2は、生活習慣病の病態形成において重要な因子であることが明らかとなったことは、増加する生活習慣病の病態解明において新たな知見であると考えられる。
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