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

Autor: 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
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Drug Delivery, Vol 24, Iss 1, Pp 558-568 (2017)
Druh dokumentu: article
ISSN: 1071-7544
1521-0464
10717544
DOI: 10.1080/10717544.2017.1279237
Popis: 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 γ-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 best-known 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.
Databáze: Directory of Open Access Journals
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