Exploration for food factor improving leptin resistance and validation of its anti-obesity action

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K00859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Osaka Prefecture University
• Principal Investigator: Akagawa Mitsugu 大阪府立大学, 生命環境科学研究科, 准教授 (70405356)
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

食品機能化学

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。