Xu Weijie, Liu Juanhong, Ma Delin, Yuan Gang, Lu Yan, Yang Yan
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
PLoS One. 2017 Feb 22;12(2):e0172477. doi: 10.1371/journal.pone.0172477. eCollection 2017.
Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight. Capsaicin-containing standard chow was also introduced to non-diabetic rats (NC+CAP). Blood glucose and insulin were monitored. The phosphorylation level of tau at individual sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blots. The results revealed that the levels of phosphorylated tau protein at sites Ser199, Ser202 and Ser396 in hippocampus of T2D+CAP group were decreased significantly, but these phospho-sites in T2D+PF group didn't show such improvements compared with T2D group. There were almost no changes in non-diabetic rats on capsaicin diet (NC+CAP) compared with the non-diabetic rats with normal chow (NC). Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either. These results demonstrated that dietary capsaicin appears to prevent the hyperphosphorylation of AD-associated tau protein by increasing the activity of PI3K/AKT and inhibiting GSK-3β in hippocampus of T2D rats, which supported that dietary capsaicin might have a potential use for the prevention of AD in T2D.
2型糖尿病（T2D）是阿尔茨海默病（AD）的一个高危因素，因为大脑中的胰岛素信号通路受损。辣椒素是一种特异性瞬时受体电位香草酸受体1（TRPV1）激动剂，已被证明可改善胰岛素抵抗。在本研究中，我们调查了膳食辣椒素是否能降低T2D患者患AD的风险。将T2D大鼠连续10天喂食含辣椒素的高脂肪（HF）饮食（T2D+CAP）。将喂食T2D+CAP组平均剂量HF饮食的配对喂养T2D大鼠（T2D+PF）纳入，以控制食物摄入量和体重降低的影响。还将含辣椒素的标准饲料引入非糖尿病大鼠（NC+CAP）。监测血糖和胰岛素水平。通过蛋白质免疫印迹法分析tau蛋白在各个位点的磷酸化水平、磷脂酰肌醇3激酶/蛋白激酶B（PI3K/AKT）和糖原合酶激酶-3β（GSK-3β）的活性。结果显示，T2D+CAP组海马中Ser199、Ser202和Ser396位点的磷酸化tau蛋白水平显著降低，但与T2D组相比，T2D+PF组的这些磷酸化位点没有显示出这样的改善。与喂食正常饲料的非糖尿病大鼠（NC）相比，喂食辣椒素饮食的非糖尿病大鼠（NC+CAP）几乎没有变化。与T2D组相比，T2D+CAP组海马中PI3K/AKT活性增加，GSK-3β活性降低，而这些变化在T2D+PF组中也未出现。这些结果表明，膳食辣椒素似乎通过增加T2D大鼠海马中PI3K/AKT的活性并抑制GSK-3β来预防AD相关tau蛋白的过度磷酸化，这支持了膳食辣椒素可能对预防T2D患者的AD具有潜在用途。
