Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Diabetes. 2012 Jun;61(6):1444-54. doi: 10.2337/db11-1498. Epub 2012 Feb 23.
Obesity-induced diabetes is associated with chronic inflammation and is considered a risk factor for neurodegeneration. We tested the hypothesis that an AMP-activated protein kinase activator, resveratrol (RES), which is known to exert potent anti-inflammatory effects, would attenuate peripheral and central inflammation and improve memory deficit in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD or an HFD supplemented with RES for 20 weeks. Metabolic parameters in serum were evaluated, and Western blot analysis and immunohistochemistry in peripheral organs and brain were completed. We used the Morris water maze test to study the role of RES on memory function in HFD-treated mice. RES treatment reduced hepatic steatosis, macrophage infiltration, and insulin resistance in HFD-fed mice. In the hippocampus of HFD-fed mice, the protein levels of tumor necrosis factor-α and Iba-1 expression were reduced by RES treatment. Choline acetyltransferase was increased, and the phosphorylation of tau was decreased in the hippocampus of HFD-fed mice upon RES treatment. In particular, we found that RES significantly improved memory deficit in HFD-fed mice. These findings indicate that RES reverses obesity-related peripheral and central inflammation and metabolic derangements and improves memory deficit in HFD-fed diabetic mice.
肥胖引起的糖尿病与慢性炎症有关，被认为是神经退行性变的一个危险因素。我们检验了这样一个假设，即 AMP 激活蛋白激酶激活剂白藜芦醇（RES）具有很强的抗炎作用，它可以减轻高脂饮食（HFD）喂养的小鼠的外周和中枢炎症，并改善记忆缺陷。C57BL/6J 小鼠喂食 HFD 或 HFD 补充 RES 20 周。评估血清中的代谢参数，并完成外周器官和大脑的 Western blot 分析和免疫组织化学。我们使用 Morris 水迷宫试验研究 RES 对 HFD 处理小鼠记忆功能的作用。RES 治疗减少了 HFD 喂养小鼠的肝脂肪变性、巨噬细胞浸润和胰岛素抵抗。在 HFD 喂养小鼠的海马体中，RES 治疗降低了肿瘤坏死因子-α和 Iba-1 表达的蛋白水平。在 HFD 喂养小鼠的海马体中，胆碱乙酰转移酶增加，tau 的磷酸化减少。特别是，我们发现 RES 显著改善了 HFD 喂养小鼠的记忆缺陷。这些发现表明 RES 逆转了肥胖相关的外周和中枢炎症以及代谢紊乱，并改善了 HFD 喂养的糖尿病小鼠的记忆缺陷。
