Neuroprotective effect of treadmill exercise against blunted brain insulin signaling, NADPH oxidase, and Tau hyperphosphorylation in rats fed a high-fat diet
Neuroprotective effect of treadmill exercise against blunted brain insulin signaling, NADPH oxidase, and Tau hyperphosphorylation in rats fed a high-fat diet
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DOI：
10.1016/j.brainresbull.2018.08.001
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发表时间：
2018-09-01
影响因子：
3.8
通讯作者：
Kang, Eun-Bum
中科院分区：
文献类型：
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作者：
Jeong, Jae-Hoon;Koo, Jung-Hoon;Kang, Eun-Bum
肥胖通过引起高血糖和胰岛素抵抗诱导氧化应激，同时通过诱导大脑胰岛素抵抗和Tau蛋白过度磷酸化导致认知和记忆下降。我们的目的是研究跑步机运动对改善这些肥胖引起的病理现象的影响。20周龄的Sprague-Dawley大鼠喂食高脂饮食（HFD） 20周，诱导肥胖。随后，大鼠进行8周的跑步机运动（逐渐增加负荷强度）。将大鼠分为三组：正常饮食组（n = 15）、hfd对照组（n = 15）和hfd跑步机组（n = 15）。我们进行了水迷宫和被动回避测试，并评估了体重、曲线下面积、胰岛素抵抗的稳态模型评估和腹部内脏脂肪/体重。Western blot检测脑胰岛素信号转导、tau过度磷酸化、NADPH氧化酶相关蛋白的表达，免疫组化检测p-Tau （Ser 202/Thr 205）和p22-phox的免疫反应性。在高脂饮食组，跑步机运动有效地挽救了脑胰岛素信号、Tau蛋白的过度磷酸化和聚集以及NADPH氧化酶的激活。此外，它改善胰岛素抵抗抑制剂，减少腹部脂肪量，抑制体重增加，并挽救学习和记忆。肥胖引起的胰岛素抵抗会导致认知能力下降，如学习和记忆能力下降，但研究发现，跑步机锻炼等体育活动通过改善这些病理现象，对大脑功能有积极影响。因此，我们建议在代谢和神经退行性疾病的预防和治疗中必须考虑跑步机运动。
Obesity induces oxidative stress by causing hyperglycemia and insulin resistance, while contributing to cognitive and memory decline by inducing insulin resistance in the brain and hyperphosphorylation of Tau proteins. We aimed to investigate the effects of treadmill exercise in improving these obesity-induced pathological phenomena. Sprague-Dawley rats aged 20 weeks were fed a high-fat diet (HFD) for 20 weeks to induce obesity. The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks. The rats were divided into three groups: normal diet-control (n = 15), HFD-control (n = 15), and HFD-treadmill exercise (n = 15). We performed water maze and passive avoidance tests and assessed weight, area under the curve, homeostatic model assessment of insulin resistance, and abdominal visceral fat/body weight. Western blot was used to examine protein expression related to brain insulin signaling, tau hyperphosphorylation, and NADPH oxidase, and immunohistochemistry was performed to examine the immunoreactivity of p-Tau (Ser 202/Thr 205) and p22-phox. Treadmill exercise effectively rescued brain insulin signaling, hyperphosphorylation and aggregation of Tau protein, and NADPH oxidase activation in the high fat diet group. Furthermore, it improved insulin resistance inhibitors, decreased abdominal fat mass, inhibited weight gain, and rescued learning and memory. Obesity-induced insulin resistance contributes to cognitive decline, such as reduced learning and memory, but physical activity, such as treadmill exercise, was found to have a positive effect on brain function by improving thesepathological phenomena. Therefore, we suggest that treadmill exercise must be considered in the prevention and treatment of metabolic and neurodegenerative diseases.