Effects of treadmill exercise on PI3K/AKT/GSK-3β pathway and tau protein in high-fat diet-fed rats

Abstract

[Purpose]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.[Methods]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.[Results]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.[Conclusion]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.

Diabetic phenotype in mouse and humans reduces the number of microglia around β-amyloid plaques

“…Thus, decreased phosphorylation of the inhibitory S9 site in Gsk3β upon TWD may explain the increased number of AT8-positive dystrophic neurites observed in our study. Supporting this idea, increased phosphorylation of Tau due to HFD or TWD in mice and rats has been observed also previously [16,84,100]. On the other hand, our biochemical analysis did not reveal clear changes in the levels of phosphorylated or total Tau by the TWD, which might be due to limited solubility of aggregated Tau protein with the extraction method used.…”

Mori Cortex Radicis Attenuates High Fat Diet-Induced Cognitive Impairment via an IRS/Akt Signaling Pathway

“…PI3K/Akt also regulate Tau (microtubule binding protein), a key player in the pathogenesis of Alzheimer's disease [2]. Reduced PI3K and p-Akt activate GSK3β inducing Tau over-phosphorylation.…”

“…Obesity is generally believed to be caused by excessive eating and environmental and genetic factors and is considered a low-grade inflammatory disease [1]. However, obesity is a component of metabolic disorders such as dyslipidemia, insulin resistance, hyperlipidemia, hypertension, and type 2 diabetes (T2DM) [2]. In particular, type 2 diabetes induces insulin resistance, oxidative stress, inflammation, and aging [3].…”

Chinese nutraceuticals and physical activity; their role in neurodegenerative tauopathies

“…Additionally, Um et al [ 264 ] for seventeen months, measured Aβ, noticing impact of exercise on decreased Aβ 1–42 deposition. Following physical activity and exercise, it has been reported from many animal studies that there is reduction in phosphorylation of tau present in brain and tau pathology [ 265 – 269 ], and reduction in hippocampal tau pathology [ 266 , 267 , 270 ] using intervention varying from 2 to 5 months and 2–9 months have been observed from studies. In the effect of physical activity and exercise on brain tau, it is uncertain whether specific aspects of intervention involve in a key function from the findings made.…”