Abstract
Cognitive dysfunction is an important complicated disease in obesity. Exercise ameliorates obesity and the related cognitive dysfunction. However, the underlying mechanism is still unclear. In this study, we investigated whether aerobic interval training (AIT) could attenuate high-fat-diet- (HFD-) associated cognitive dysfunction and the possible mechanism of SIRT3-MnSOD pathway. C57BL/6 wild-type (WT) mice and SIRT3 knockout (KO) mice were randomized into control (Con) or HFD group with or without AIT training for 6 weeks. The spatial learning and memory ability were impaired in HFD group compared to the control group. The levels of mitochondrial protein acetylation were increased in the hippocampus of HFD group. The acetylation level of antioxidative MnSOD was increased as well. As a result, the ROS and MDA levels were significantly increased, which leads to the neuron apoptosis in the hippocampus. SIRT3 deficiency further aggravated HFD-induced cognitive dysfunction and susceptibility to oxidative stress injury. However, AIT upregulated neuron SIRT3 expression and decreased the acetylation of MnSOD. The hippocampus neuron oxidative stress and apoptosis were both decreased compared to untrained HFD group, which finally improved cognitive function of HFD mice. Collectively, AIT attenuates HFD-associated cognitive dysfunction through SIRT3 upregulation and improvement of antioxidative MnSOD activity.
Highlights
High-fat diet (HFD) is one of the main factors of obesity in modern society [1]
We newly found that Aerobic interval training (AIT) can effectively improve HFD-related cognitive dysfunction
The spatial learning and memory functions in HFD-SIRT3 KO mice were seriously declined (Figures 1(b) and 1(c)). These data indicated that high-fat diet leads to impaired cognitive function, which is more evident in the SIRT3 deficiency mice
Summary
High-fat diet (HFD) is one of the main factors of obesity in modern society [1]. Obesity, as a metabolic disease, manifests the excessive fat accumulation and increased body weight. Exercise training has been recognized to exert beneficial effects in obese individuals. Clinical studies and animal experiments have shown that exercise training reduces body weight and ameliorates brain dysfunction [7]. AIT may provide an effective and time-efficient alternative to improve physical condition. It remains unclear whether AIT would protect against cognitive dysfunction in HFD individuals. We newly found that AIT can effectively improve HFD-related cognitive dysfunction. SIRT3 is an important regulator that mediates neuroprotective effect of AIT in HFD individual via the antioxidative MnSOD in hippocampus neurons. There results may provide novel insight into exercise therapy in HFD-induced cognitive dysfunction
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