| Project/Area Number |
16K00859
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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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| Research Field |
Eating habits
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Akagawa Mitsugu 大阪府立大学, 生命環境科学研究科, 准教授 (70405356)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | レプチン / 肥満 / イソチオシアネート / レプチンシグナル / 抗肥満 / 食品因子 / レプチン抵抗性 / 機能性食品 |
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| Outline of Final Research Achievements |
Obesity is a growing and serious health problem worldwide. Leptin is a weight-reducing hormone, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and JAK2/STAT3 signaling. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. We revealed that phenethyl isothiocyanate (PEITC), an isothiocyanate in certain cruciferous vegetables, potently inhibits PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in human SH-SY5Y neuronal cells. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、アブラナ科野菜に含まれるphenethyl isothiocyanate (PEITC) が、PTP1B活性を阻害し、レプチンシグナルをリガンド非依存的に活性化することを見出した。さらに動物レベルでPEITCがレプチンシグナルを活性化して摂食抑制作用を示すことを明らかにした。本成果は、食品因子によるレプチンシグナルの制御という新たな食品の機能性を初めて実証したものである。本成果を応用することによって、肥満を発症基盤とする多くの生活習慣病の予防・改善にも貢献しうることから、 国民生活への反映、および波及効果は、極めて大きいと考える。
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