Brown rice and its component, γ-oryzanol, attenuate the preference for high-fat diet by decreasing hypothalamic endoplasmic reticulum stress in mice.
Brown rice and its component, γ-oryzanol, attenuate the preference for high-fat diet by decreasing hypothalamic endoplasmic reticulum stress in mice.
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DOI：
10.2337/db11-1767
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发表时间：
2012-12
期刊：
影响因子：
7.7
通讯作者：
Masuzaki H
中科院分区：
文献类型：
--
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
众所周知，糙米可以改善葡萄糖耐受不良，预防糖尿病的发生。然而，潜在的机制仍然不清楚。本文研究了糙米及其主要成分γ-谷维素（Orz）对小鼠摄食行为和能量平衡的影响。当小鼠被允许自由进入含有糙米的食物饮食（CD）和高脂肪饮食（HFD）时，它们明显更喜欢CD而不是HFD。为了减少下丘脑内质网（ER）对HFD的应激，给小鼠施用4-苯基丁酸（一种化学伴侣），这使它们更喜欢CD。值得注意的是，口服Orz（糙米中主要生物活性成分的混合物）也改善了喂食HFD的小鼠的葡萄糖耐受不良和减弱了下丘脑ER应激。在小鼠原代神经元细胞中，Orz减弱衣霉素诱导的ER应激。在人胚肾293细胞中的荧光素酶报告基因测定中，Orz抑制ER应激反应顺式作用元件和未折叠蛋白反应元件的激活，表明Orz在活细胞中充当化学伴侣。总的来说，目前的研究是第一次证明糙米和Orz可以改善葡萄糖代谢，减少下丘脑ER应激，从而减弱喂食HFD的小鼠对膳食脂肪的偏好。
Brown rice is known to improve glucose intolerance and prevent the onset of diabetes. However, the underlying mechanisms remain obscure. In the current study, we investigated the effect of brown rice and its major component, γ-oryzanol (Orz), on feeding behavior and fuel homeostasis in mice. When mice were allowed free access to a brown rice–containing chow diet (CD) and a high-fat diet (HFD), they significantly preferred CD to HFD. To reduce hypothalamic endoplasmic reticulum (ER) stress on an HFD, mice were administered with 4-phenylbutyric acid, a chemical chaperone, which caused them to prefer the CD. Notably, oral administration of Orz, a mixture of major bioactive components in brown rice, also improved glucose intolerance and attenuated hypothalamic ER stress in mice fed the HFD. In murine primary neuronal cells, Orz attenuated the tunicamycin-induced ER stress. In luciferase reporter assays in human embryonic kidney 293 cells, Orz suppressed the activation of ER stress–responsive cis-acting elements and unfolded protein response element, suggesting that Orz acts as a chemical chaperone in viable cells. Collectively, the current study is the first demonstration that brown rice and Orz improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice fed an HFD.
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