| Project/Area Number |
18K15766
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脂肪性肝疾患 / オートファジー / 非アルコール性脂肪性肝疾患 / SERCA |
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| Outline of Final Research Achievements |
Autophagy is suppressed in the liver of non-alcoholic fatty liver disease (NAFLD) and is thought to contribute to the pathogenesis of the disease. We analyzed the effects of free fatty acids on autophagy in hepatocytes and found that, unlike unsaturated fatty acids, saturated fatty acids inhibit the fusion of autophagosomes and lysosomes, and that this defect is correlated with endoplasmic reticulum stress. We also found that a decrease in calcium concentration in the endoplasmic reticulum was the main factor, and that SERCA, a calcium transport protein, was involved. Therefore, we expected SERCA activators to ameliorate autophagy impairment caused by saturated fatty acids, but unfortunately, we did not find such an effect.
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| Academic Significance and Societal Importance of the Research Achievements |
「遊離脂肪酸とオートファジー」の研究は肝領域のみならず様々な領域でなされているが、現在のところ、オートファジーを促進する化合物はあるものの、超選択的に促進する化合物はなく、ヒトの疾患でオートファジーをターゲットにした治療は限られている。本研究によりオートファジーの障害機序を明らかにすることで「オートファジーの誘導」ではなく、「障害されたオートファジー機能の回復」という新たな治療戦略の基盤作りが可能となることを期待している。現在食事療法や運動療法が主体であるNASHにおいても、本研究によってオートファジーのメカニズムがさらに理解されれば、NASH治療の一助になると考える。
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