Aerobic Interval Training Regulated SIRT3 Attenuates High-Fat-Diet-Associated Cognitive Dysfunction

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.

Exercise and Sirtuins: A Way to Mitochondrial Health in Skeletal Muscle

“…However, aerobic interval training attenuated neuronal apoptosis and improved cognitive function in mice with HFD through the positive regulation of the SIRT3-MnSOD pathway, and the reduction of oxidative stress levels. These findings would place SIRT3 as a new factor in the neuroprotective field [18].…”

Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis

“…According to the evidence on the neuroprotective effect of SIRT3 during exercise, Shi and colleagues demonstrated that aerobic interval training (AIT)-induced SIRT3 expression decreased OS generated by HFD, thereby improving cognitive function [55]. The authors reported that HFD significantly compromised cognitive function in mice and particularly in SIRT3-deficient mice [55], remarking that alterations in glucose and lipid metabolisms are noxious for vital organs. Moreover, HFD increased acetylation levels of several proteins in the hippocampus; among those, MnSOD became iper-acetylated and was unable to blunt ROS production [55].…”

“…The authors reported that HFD significantly compromised cognitive function in mice and particularly in SIRT3-deficient mice [55], remarking that alterations in glucose and lipid metabolisms are noxious for vital organs. Moreover, HFD increased acetylation levels of several proteins in the hippocampus; among those, MnSOD became iper-acetylated and was unable to blunt ROS production [55]. Subsequently, mice fed with HFD were subjected to AIT for 6 weeks, showing an increase in SIRT3, which, in turn, deacetylated MnSOD and reduced OS [55].…”

“…Moreover, HFD increased acetylation levels of several proteins in the hippocampus; among those, MnSOD became iper-acetylated and was unable to blunt ROS production [55]. Subsequently, mice fed with HFD were subjected to AIT for 6 weeks, showing an increase in SIRT3, which, in turn, deacetylated MnSOD and reduced OS [55]. Furthermore, AIT improved spatial cognition and memory ability in HFD-induced obese mice [55].…”

The Effect of High-Intensity Interval Training with and Without Caloric Restriction on Spatial Learning and Long-Term Memory of Obese Rats

“…Sport exercises, like the CR, reduce overweight, obesity, and related disorders by activating countless signaling pathways. In a study, Shi et al stated that interval training by regulating sirtuin-3 (SIRT3) could reduce the cognitive dysfunction associated with HFD (20). Physical activity is also recognized as an effective method for improving the cognitive function of all age groups, especially the elderly who are more susceptible to neurological disorders since the release of mycoses by the operating muscles leads to the upregulation of neurotrophin expression in the hippocampal dentate gyrus (12).…”