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

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)558-568
    Number of pages11
    JournalDrug Delivery
    Volume24
    Issue number1
    DOIs
    Publication statusPublished - Feb 9 2017

    All Science Journal Classification (ASJC) codes

    • Pharmaceutical Science

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