Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

The glymphatic system as a nexus between obesity and neurological diseases

Nature Reviews Endocrinology volume 21, pages 1–2 (2025)Cite this article

Subjects

Exploring the glymphatic system across neurological and metabolic diseases might help us to better define the link between obesity and neurological disorders. Recent studies have identified metabolic dysfunction as a risk factor for cognitive decline and neurological disorders through disruption of the glymphatic system.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Domino effect of cerebral rewiring.

References

  1. Tian, S. et al. Association between body mass index and glymphatic function using diffusion tensor image-along the perivascular space (DTI-ALPS) in patients with Parkinson’s disease. Quant. Imaging Med. Surg. 14, 2296–2308 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Munis, O. B. Association of type 2 diabetes mellitus with perivascular spaces and cerebral amyloid angiopathy in Alzheimer’s disease: insights from MRI imaging. Dement. Neurocognitive Disord. 22, 87–99 (2023).

    Article  Google Scholar 

  3. Zhan, M. et al. Promotion of neuroinflammation by the glymphatic system: a new insight into ethanol extracts from Alisma orientale in alleviating obesity-associated cognitive impairment. Phytomedicine 122, 155147 (2024).

    Article  CAS  PubMed  Google Scholar 

  4. Yuan, Y. et al. AQP4 endocytosis-lysosome degradation mediated by MMP-9/β-DG involved in diabetes cognitive impairment. Mol. Neurobiol. https://doi.org/10.1007/s12035-024-04085-9 (2024).

  5. Huang, H. et al. A four-week high-fat diet induces anxiolytic-like behaviors through mature BDNF in the mPFC of mice. Brain Sci 14, 389 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Deng, J., Zhang, J., Feng, C., Xiong, L. & Zuo, Z. Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice. Cardiovasc. Res. 103, 473–484 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Si, X. et al. Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson’s disease. J. Adv. Res. 56, 125–136 (2024).

    Article  CAS  PubMed  Google Scholar 

  8. Tomassoni, D. et al. Obesity and age-related changes in the brain of the Zucker Leprfa/fa rats. Nutrients 12, 1356 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Micioni Di Bonaventura, M. V. et al. Brain alterations in high fat diet induced obesity: effects of tart cherry seeds and juice. Nutrients 12, 623 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ward, R. et al. NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia. Pharmacol. Res. 142, 237–250 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

M.S. acknowledges support from the McCluskey family and Interstellar Initiative (NYAS/AMED) and the National Institute of Diabetes, Digestive and Kidney Diseases. J.-L.T. acknowledges the US National Institutes of Health and Monitoring Neuroinflammation supported by the French Fonds Recherche Neurosciences.

Author information

Authors and Affiliations

  1. Laboratory of Neurovascular Control of Homeostasis, Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA

    Bandy Chen & Marc Schneeberger

  2. Department of Neuroradiology, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France

    Stephanie Lenck

  3. Institut du Cerveau, Pitié-Salpêtrière Hospital, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Sorbonne Université, Paris, France

    Stephanie Lenck & Jean-Leon Thomas

  4. Department of Neurology, Yale School of Medicine, New Haven, CT, USA

    Jean-Leon Thomas

  5. Wu Tsai Institute for Mind and Brain, Yale University, New Haven, CT, USA

    Marc Schneeberger

Authors
  1. Bandy Chen
    View author publications

    Search author on:PubMed Google Scholar

  2. Stephanie Lenck
    View author publications

    Search author on:PubMed Google Scholar

  3. Jean-Leon Thomas
    View author publications

    Search author on:PubMed Google Scholar

  4. Marc Schneeberger
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Bandy Chen or Marc Schneeberger.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, B., Lenck, S., Thomas, JL. et al. The glymphatic system as a nexus between obesity and neurological diseases. Nat Rev Endocrinol 21, 1–2 (2025). https://doi.org/10.1038/s41574-024-01042-3

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41574-024-01042-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing