Abstract: BACKGROUND: Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease, but also closely related to the increased risk of cognitive decline, dementia and other neurodegenerative diseases. Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment, but their therapeutic effects and related mechanisms of action are still unclear.
OBJECTIVE: To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.
METHODS: Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups: a control group was fed normally for 20 weeks; a high fat group was fed with high fat diet (60% fat energy) for 20 weeks; an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise; and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise. After the exercise intervention, body mass was weighed, insulin tolerance and glucose tolerance were tested to evaluate insulin resistance, and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment. The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining. The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR, and the protein expressions of Bax , Bcl-2, nuclear factor-κB, Cleaved Caspase-1, Caspase-3, synapsin 1 and brain-derived neurotrophic factor were detected by western blot.
RESULTS AND CONCLUSION: (1) Compared with the control group, the body mass of mice increased in the high-fat group (P < 0.05), accompanied by insulin resistance and cognitive dysfunction, the expression levels of nuclear factor-κB, Bax, Caspase-3, Cleaved Caspase-1 in the hippocampus were significantly increased (P < 0.05), the expression levels of brain-derived neurotrophic factor, synapsin 1 and Bcl-2 proteins were significantly decreased (P < 0.05), Bcl-2/Bax ratio was significantly decreased (P < 0.05), and the mRNA levels of inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were significantly up-regulated (P < 0.05). (2) Compared with the high-fat group, the above indexes were significantly improved in the aerobic exercise group (P < 0.05), while in the resistance exercise group, the body mass of mice was significantly decreased, the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased (P < 0.05), the protein expression of Caspase-3 was significantly decreased (P < 0.05), and the protein expression of brain-derived neurotrophic factor was significantly up-regulated (P < 0.05), but no significant changes were observed in the other indexes (P > 0.05). In conclusion, long-term exercise can reduce insulin resistance, down-regulate the expression of nuclear factor-κB pathway, weaken inflammatory response, inhibit neuronal apoptosis and improve synaptic plasticity, resulting in neuroprotective effects, and effectively alleviate obesity-related cognitive dysfunction in obese mice. The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

Key words: obesity-related cognitive impairment, nuclear factor-κB, aerobic exercise, resistance exercise, neuroinflammation, synaptic plasticity, apoptosis, engineered tissue construction