Jeong Jae-Hoon, Kang Eun-Bum
J Exerc Nutrition Biochem. 2018 Mar 30;22(1):9-14. doi: 10.20463/jenb.2018.0002.
This study aimed to clearly evaluate the effects of obesity on cerebral health. Thus, we induced obesity in rats using a long-term high-fat diet (HFD), then investigated its effects on insulin signaling and tau hyperphosphorylation. Additionally, we examined the effects of 8 weeks of treadmill exercise (TE) on insulin signaling and tau hyperphosphorylation.
Rats were separated into Normal Diet-Control, HFD-Control, and HFD-TE groups. TE loads were gradually increased. A passive avoidance test was used to evaluate cognitive function. Western blots were used to examine the abundance of the insulin receptor,phosphoinositide 3-kinase, protein kinase B, glycogen synthase kinase-3β, and tau proteins in the cerebral cortex; immunohistochemical analyses were used to examine the abundance of hyperphosphorylated tau in the cerebral cortex.
TE in HFD-fed rats resulted in a significant lowering of bodyweight, abdominal visceral fat (AVF), the area under the glucose response curve, and the homeostatic model assessment-insulin resistance index, while it improved working memory. In addition, TE in HFD-fed rats decreased tau hyperphosphorylation and aggregation, while increasing insulin signaling-related protein activity.
After a 20-week HFD, the experimental animals exhibited increased weight, as well as impaired insulin resistance and blood glucose metabolism. HFD rats demonstrated abnormal insulin signaling and tau hyperphosphorylation in the cerebral cortex, as well as memory impairments that suggested reduced cerebral function. However, TE reduced AVF, improved insulin resistance in the peripheral tissues by increasing insulin sensitivity, and alleviated memory impairments by restoring insulin signaling and reducing tau hyperphosphorylation in the cerebral cortex.
本研究旨在明确评估肥胖对大脑健康的影响。因此，我们使用长期高脂饮食（HFD）诱导大鼠肥胖，然后研究其对胰岛素信号传导和tau蛋白过度磷酸化的影响。此外，我们还研究了8周跑步机运动（TE）对胰岛素信号传导和tau蛋白过度磷酸化的影响。
将大鼠分为正常饮食对照组、高脂饮食对照组和高脂饮食运动组。逐渐增加运动负荷。采用被动回避试验评估认知功能。用蛋白质免疫印迹法检测大脑皮质中胰岛素受体、磷脂酰肌醇3激酶、蛋白激酶B、糖原合酶激酶-3β和tau蛋白的丰度；用免疫组织化学分析检测大脑皮质中过度磷酸化tau蛋白的丰度。
高脂饮食喂养大鼠进行运动可显著降低体重、腹部内脏脂肪（AVF）、葡萄糖反应曲线下面积和稳态模型评估胰岛素抵抗指数，同时改善工作记忆。此外，高脂饮食喂养大鼠进行运动可减少tau蛋白过度磷酸化和聚集，同时增加胰岛素信号相关蛋白活性。
经过20周的高脂饮食后，实验动物体重增加，胰岛素抵抗和血糖代谢受损。高脂饮食大鼠大脑皮质出现胰岛素信号异常和tau蛋白过度磷酸化，以及提示大脑功能减退的记忆障碍。然而，运动减少了腹部内脏脂肪，通过提高胰岛素敏感性改善了外周组织的胰岛素抵抗，并通过恢复胰岛素信号传导和减少大脑皮质中tau蛋白过度磷酸化缓解了记忆障碍。
