Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice.
Marked augmentation of PLGA nanoparticle-induced metabolically beneficial impact of γ-oryzanol on fuel dyshomeostasis in genetically obese-diabetic ob/ob mice.
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DOI：
10.1080/10717544.2017.1279237
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Masuzaki H
中科院分区：
文献类型：
--
作者：
Kozuka C;Shimizu-Okabe C;Takayama C;Nakano K;Morinaga H;Kinjo A;Fukuda K;Kamei A;Yasuoka A;Kondo T;Abe K;Egashira K;Masuzaki H
我们的前期工作表明，糙米特异性生物活性物质γ-谷维素作为一种分子伴侣，可以减轻高脂饮食诱导的肥胖糖尿病小鼠脑下丘脑和胰岛中过度的内质网（ER）应激，从而改善其代谢紊乱。然而，γ-谷维素在肠道的吸收效率极低，是其临床应用的一坚韧障碍。因此，在本研究中，为了克服具有超高亲脂性的γ-谷维素的极低生物利用度，我们将γ-谷维素包封在聚合物聚（DL-丙交酯-共-乙交酯）（PLGA）纳米颗粒（Nano-Orz）中，并评估其在遗传性肥胖糖尿病ob/ob小鼠（最知名的小鼠最易患糖尿病模型）中的代谢有益影响。令我们惊讶的是，与常规的γ-谷维素相比，Nano-Orz显著改善了燃料代谢，其程度出乎意料（剂量低1000倍）。此外，每2周给药一次即可达到如此显著的效果。除了对下丘脑和胰岛功能障碍的良好影响外，Nano-Orz还显著降低了肝脏和脂肪组织中的ER应激和炎症。总的来说，以γ-谷维素为导向的功能性食品的纳米技术开发为治疗人类各种代谢疾病提供了新的方法。
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.
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影响因子：
7.7
作者：
Kozuka C;Yabiku K;Sunagawa S;Ueda R;Taira S;Ohshiro H;Ikema T;Yamakawa K;Higa M;Tanaka H;Takayama C;Matsushita M;Oyadomari S;Shimabukuro M;Masuzaki H
通讯作者：
Masuzaki H
影响因子：
3.7
作者：
Kamei A;Watanabe Y;Kondo K;Okada S;Shinozaki F;Ishijima T;Nakai Y;Kondo T;Arai S;Abe K
通讯作者：
Abe K
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
5.5
作者：
Navarro, Sara M.;Morgan, Timothy W.;Sabliov, Cristina M.
通讯作者：
Sabliov, Cristina M.
DOI：
10.1056/nejmoa1014296
发表时间：
2011-06-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Mozaffarian D;Hao T;Rimm EB;Willett WC;Hu FB
通讯作者：
Hu FB