Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Diabetes. 2012 Dec;61(12):3084-93. doi: 10.2337/db11-1767. Epub 2012 Jul 23.
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.
糙米被认为可以改善葡萄糖不耐受并预防糖尿病的发生。然而，其潜在机制尚不清楚。在本研究中，我们研究了糙米及其主要成分γ-谷维素（Orz）对小鼠摄食行为和燃料稳态的影响。当小鼠被允许自由选择含有糙米的饲料（CD）和高脂肪饲料（HFD）时，它们明显更喜欢 CD 而不是 HFD。为了减少 HFD 下下丘脑内质网（ER）应激，给小鼠施用了 4-苯丁酸，一种化学伴侣，这导致它们更喜欢 CD。值得注意的是，口服糙米中的主要生物活性成分混合物 Orz，也改善了 HFD 喂养小鼠的葡萄糖不耐受，并减轻了下丘脑 ER 应激。在原代小鼠神经元细胞中，Orz 减轻了衣霉素诱导的 ER 应激。在人胚肾 293 细胞的荧光素酶报告基因检测中，Orz 抑制了 ER 应激反应元件和未折叠蛋白反应元件的激活，表明 Orz 在活细胞中作为一种化学伴侣发挥作用。总的来说，本研究首次证明糙米和 Orz 可以改善葡萄糖代谢，减轻下丘脑 ER 应激，从而减少 HFD 喂养小鼠对膳食脂肪的偏好。
