High fat diet induces brain insulin resistance and cognitive impairment in mice
High fat diet induces brain insulin resistance and cognitive impairment in mice
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DOI：
10.1016/j.bbadis.2016.10.006
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发表时间：
2017-02-01
影响因子：
6.2
通讯作者：
Babu, Jeganathan Ramesh
中科院分区：
文献类型：
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作者：
Kothari, Vishal;Luo, Yuwen;Babu, Jeganathan Ramesh
高脂饮食诱导的肥胖与胰岛素抵抗(IR)和其他慢性饮食相关疾病有关，包括痴呆症。阿尔茨海默病是最常见的痴呆症，其特征是大脑中存在淀粉样斑块和神经原纤维缠结。这项研究旨在确定饮食诱导的外周胰岛素敏感性变化是否会导致大脑胰岛素信号和认知功能的变化。6周龄雄性C57BL/6NHsd小鼠随机分为高脂饲料(脂肪能量40%)和普通饲料(脂肪能量12%)两组，每组14周。代谢表型包括能量消耗、体力活动、食物摄入量、葡萄糖和胰岛素耐量试验。此外，我们还检测了与脑胰岛素信号和认知功能相关的蛋白质表达的变化。与喂食正常饮食的老鼠相比，喂食HFS的小鼠在肥胖、葡萄糖和胰岛素耐受性方面表现出显著的统计学意义。在脑内，HFS引起IR，表现为胰岛素受体酪氨酸磷酸化显著降低，IRS-1丝氨酸磷酸化增加。伴随这些变化的是全脑裂解液中的炎性反应(核因子kappaB，JNK)和应激反应(p38MAPK，CHOP)。此外，HFS小鼠大脑表现出与淀粉样β蛋白沉积增加和神经纤维缠结形成有关的生化变化，并降低了突触可塑性。这些结果表明，胰岛素敏感性的变化可能导致与HFS饮食相关的小鼠认知障碍。(C)2016年，由爱思唯尔出版。
High fat diet-induced obesity is associated with insulin resistance (IR) and other chronic, diet related illnesses, including dementia. Alzheimer disease is the most common form of dementia, and is characterized by the presence of amyloid plaques and neurofibrillary tangles in brain. This study was designed to determine whether diet induced changes in peripheral insulin sensitivity could contribute to alterations in brain insulin signaling and cognitive functions. Six week old, male C57BL/6NHsd mice were randomly assigned a high fat diet (40% energy from fat) with 42 g/L liquid sugar (HFS) added to the drinking water or a normal chow diet (12% energy from fat) for 14 weeks. Metabolic phenotypes were characterized for energy expenditure, physical activity, and food intake, and glucose and insulin tolerance tests. In addition, we examined the changes in protein expression related to brain insulin signaling and cognitive function. Mice fed HFS exhibited a statistically significant increase in obesity, and lower glucose and insulin tolerance as compared to animals fed the normal chow diet. In brain, HFS elicited IR as evidenced by a significant decrease in tyrosine phosphorylation of insulin receptor and an increase serine phosphorylation of IRS-1. These changes were accompanied by inflammatory (NF kappa B, JNK) and stress responses (p38 MAPK, CHOP) in whole brain lysate. In addition, HFS mouse brain exhibited biochemical changes related to increased amyloid beta deposition and neurofibrillary tangle formation, and decreased synaptic plasticity. These results suggested changes in insulin sensitivity might contribute to cognitive impairment associated with the HFS diet in mice. (C) 2016 Published by Elsevier B.V.