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

Area of Science:

• Neuroscience
• Metabolism
• Mitochondrial Biology

Background:

• Obesity is linked to cognitive dysfunction, with mechanisms not fully understood.
• Exercise shows promise in mitigating obesity-related cognitive decline.
• The role of specific molecular pathways, like SIRT3-MnSOD, remains to be elucidated.

Purpose of the Study:

• To investigate if aerobic interval training (AIT) can reverse high-fat diet (HFD)-induced cognitive dysfunction.
• To explore the involvement of the SIRT3-MnSOD pathway in this process.

Main Methods:

• Mice (wild-type and SIRT3 knockout) were fed a high-fat diet (HFD) with or without AIT for 6 weeks.
• Spatial learning and memory were assessed.
• Mitochondrial protein acetylation, oxidative stress markers (ROS, MDA), and neuron apoptosis were measured in the hippocampus.

Main Results:

• HFD impaired spatial learning and memory, increasing hippocampal mitochondrial protein acetylation, including MnSOD.
• This led to elevated oxidative stress and neuron apoptosis.
• SIRT3 deficiency exacerbated HFD effects.
• AIT reversed cognitive decline by upregulating SIRT3, decreasing MnSOD acetylation, and reducing oxidative stress and apoptosis.

Conclusions:

• AIT effectively attenuates HFD-induced cognitive dysfunction in mice.
• The mechanism involves the SIRT3-MnSOD pathway, where AIT enhances SIRT3 activity and improves MnSOD's antioxidant function.
• This highlights AIT as a potential intervention for obesity-related cognitive impairments.