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Molecular Biology

The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity

International Journal of Obesity (2024)Cite this article

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Abstract

Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer’s disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.

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Fig. 1: Insulin and insulin signalling in the brain of obesity.
Fig. 2: The links among insulin resistance, mitochondria, and neuronal plasticity in obese brain.
Fig. 3: Graphical summary of the mitochondrial quality control system.
Fig. 4: Exercise may remedy insulin resistance in the obese brain and target brain mitochondrial quality control system to repair mitochondrial dysfunction.

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Funding

This work was sponsored by Shanghai Sailing Program (22YF1441600), the grant of the funding of Youth Fund Project of Research Planning Foundation on Humanities and Social Sciences of the Ministry of Education (20YJCZH001), the Scientific Research Foundation of SUMHS (SSF-21-03-008), the Project of Key Medical Discipline Group Construction in Shanghai Pudong New Area (No. PWZxq2022-13) and the Project of Clinical Outstanding Discipline Construction in Shanghai Pudong New Area (No. PWYgy2021-09).

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Author notes

  1. These authors contributed equally: Ming Cai, Jian Wan, Keren Cai.

Authors and Affiliations

  1. Jinshan District Central Hospital affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, 201599, China

    Ming Cai

  2. Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People’s Hospital, Shanghai, 201299, China

    Jian Wan

  3. College of Rehabilitation Sciences, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China

    Keren Cai, Shuyao Li & Xinlin Du

  4. Central Lab, Shanghai Key Laboratory of Pathogenic Fungi Medical Testing, Shanghai Pudong New Area People’s Hospital, Shanghai, 201299, China

    Haihan Song, Wanju Sun & Jingyun Hu

Authors
  1. Ming Cai
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  2. Jian Wan
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  3. Keren Cai
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  4. Shuyao Li
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  5. Xinlin Du
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  6. Haihan Song
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  7. Wanju Sun
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  8. Jingyun Hu
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Contributions

Ming Cai, Jian Wan, and Kenren Cai is the co-first authors. They drafted the manuscript and contributed equally to this article. Shuyao Li, Xinlin Du, and Haihan Song assisted with drafting the tables and figures. Wanju Sun and Jingyun Hu conceptualized the article and revised the final version. All authors read and approved the final manuscript.

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Correspondence to Wanju Sun or Jingyun Hu.

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Cai, M., Wan, J., Cai, K. et al. The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01490-x

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  • DOI: https://doi.org/10.1038/s41366-024-01490-x

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