Marked augmentation of plga nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice

Chisayo Kozuka, Chigusa Shimizu-Okabe, Chitoshi Takayama, Kaku Nakano, Hidetaka Morinaga, Ayano Kinjo, Kotaro Fukuda, Asuka Kamei, Akihito Yasuoka, Takashi Kondo, Keiko Abe, Kensuke Egashira, Hiroaki Masuzaki

    研究成果: ジャーナルへの寄稿学術誌査読

    34 被引用数 (Scopus)

    抄録

    Our previous works demonstrated that brown rice-specific bioactive substance, γ-oryzanol acts as a chaperone, attenuates exaggerated endoplasmic reticulum (ER) stress in brain hypothalamus and pancreatic islets, thereby ameliorating metabolic derangement in high fat diet (HFD)-induced obese diabetic mice. However, extremely low absorption efficiency from intestine of γ-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of γ-oryzanol with super-high lipophilicity, we encapsulated g-oryzanol in polymer poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Nano-Orz), and evaluated its metabolically beneficial impact in genetically obese-diabetic ob/ob mice, the bestknown severest diabetic model in mice. To our surprise, Nano-Orz markedly ameliorated fuel metabolism with an unexpected magnitude (∼1000-fold lower dose) compared with regular γ-oryzanol. Furthermore, such a conspicuous impact was achievable by its administration once every 2 weeks. Besides the excellent impact on dysfunction of hypothalamus and pancreatic islets, Nano-Orz markedly decreased ER stress and inflammation in liver and adipose tissue. Collectively, nanotechnology-based developments of functional foods oriented toward γ-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.

    本文言語英語
    ページ(範囲)558-568
    ページ数11
    ジャーナルDrug Delivery
    24
    1
    DOI
    出版ステータス出版済み - 2月 9 2017

    !!!All Science Journal Classification (ASJC) codes

    • 薬科学

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