Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease
Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease
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DOI：
10.1074/jbc.m703561200
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发表时间：
2007-12-14
影响因子：
4.8
通讯作者：
Li, Ling
中科院分区：
文献类型：
--
作者：
Cao, Dongfeng;Lu, Hailin;Li, Ling
令人信服的证据表明，过量饮用含糖饮料在肥胖的流行中起着重要作用，肥胖是2型糖尿病的主要危险因素。2型糖尿病与阿尔茨海默病（AD）的高发病率有关。高脂肪饮食促进小鼠ad样病理。目前尚不清楚在正常饮食的情况下摄入过量的糖（如高热量甜饮料）是否会影响AD的发展。在本研究中，我们给转基因AD小鼠模型提供10%的蔗糖糖水，并给予正常的啮齿动物饮食。与没有在水中添加蔗糖的对照组小鼠相比，蔗糖组的体重增加更多，并出现葡萄糖耐受不良、高胰岛素血症和高胆固醇血症。这些代谢变化与记忆障碍的加剧和大脑中不溶性淀粉样蛋白水平和沉积的2 -3倍增加有关。我们进一步发现β淀粉样蛋白前体蛋白的表达水平和分泌酶裂解产物不受蔗糖摄入量的影响。胰岛素降解酶的稳态水平没有显著变化，而脑载脂蛋白e水平增加了2.5倍。因此，我们得出结论，apoE的上调加速了A β的聚集，导致蔗糖处理小鼠脑淀粉样变性恶化。这些数据强调了膳食糖在阿尔茨海默病发病机制中的潜在作用，并表明控制含糖饮料的消费可能是降低患阿尔茨海默病风险的有效途径。
Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote AD-like pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2 -3-fold increase in insoluble amyloid-beta protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-beta precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of A beta, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.