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

Our previous works demonstrated that brown rice-specific bioactive substance, gamma-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 gamma-oryzanol is a tough obstacle for the clinical application. Therefore, in this study, to overcome extremely low bioavailability of gamma-oryzanol with super-high lipophilicity, we encapsulated gamma-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 (similar to 1000-fold lower dose) compared with regular gamma-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 gamma-oryzanol shed light on the novel approach for the treatment of a variety of metabolic diseases in humans.