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Time-restricted feeding modulates neuron-glial interactions and circadian rhythm in the spinal cord of male Wistar rats fed a high-fat diet

Spinal Cord volume 63, pages 437–443 (2025)Cite this article

Subjects

Abstract

Study Design

This study utilized male Wistar rats to investigate the effects of time-restricted feeding (TRF) on high-fat diet (HFD)-induced alterations in neuron-glial interactions and gene expression levels in the spinal cord (T5-T9).

Objectives

To evaluate whether TRF mitigates HFD-induced alterations in microglial morphology, astrocyte numbers, perineuronal net (PNN) integrity, purinergic receptor expression, inflammation and circadian rhythm-related gene expression in the spinal cord.

Setting

Amsterdam University Medical Centers, location AMC, The Netherlands.

Methods

Male Wistar rats were initially fed either a standard chow diet or a HFD ad libitum for 4 weeks. After this period, rats in the HFD group were further divided into two subgroups: continued HFD ad libitum or HFD with TRF for an additional 4 weeks. Rats in the chow group continued with ad libitum feeding throughout the experimental period. At the end of the intervention, spinal cords (T5–T9) were collected for analysis. Microglial morphology, astrocyte cell numbers, and PNN integrity were assessed in the spinal cord. Expression levels of purinergic receptors, inflammation and clock genes were analyzed to investigate neuron-glial interactions and circadian rhythm stabilization.

Results

TRF reduced microglial activation, preserved PNN integrity, suppressed HFD-induced upregulation of purinergic receptors, and stabilized circadian clock gene expression.

Conclusions

These findings suggest that TRF is a promising non-pharmacological strategy to counteract obesogenic diet-induced perineuronal net degradation and neuroinflammation, highlighting its potential as a lifestyle-based intervention for pain management.

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Fig. 1: Effects of time-restricted feeding on WFA expression, IBA1-ir and GFAP-ir cells in the dorsal horn and intermediolateral nucleus of the spinal cord (T5-T9).
Fig. 2: The expression of receptor and inflammatory genes in the spinal cord (T5-T9).
Fig. 3: The expression of clock genes in the spinal cord (T5-T9).

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Data availability

The data used in the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We sincerely thank Nikita Korpel (Department of Population Health Sciences, Institute for Risk Assessment Sciences, Utrecht University) and Ewout Foppen (Endocrinology Lab, Amsterdam UMC) for their invaluable support with the animal study and technical assistance.

Funding

This study was sponsored by the Netherlands-Canada Type 2 Diabetes Research Consortium (ZonMW 459001021).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, The Netherlands

    Han Jiao, Jarne Jermei, Delaram Poormoghadam, Milan Dorscheidt, Sanne Wiekard, Andries Kalsbeek & Chun-Xia Yi

  2. Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, The Netherlands

    Han Jiao, Jarne Jermei, Delaram Poormoghadam, Milan Dorscheidt, Sanne Wiekard, Andries Kalsbeek & Chun-Xia Yi

  3. Department of Clinical Chemistry, Laboratory of Endocrinology, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands

    Han Jiao, Jarne Jermei, Delaram Poormoghadam, Milan Dorscheidt, Sanne Wiekard, Andries Kalsbeek & Chun-Xia Yi

  4. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands

    Han Jiao, Jarne Jermei, Delaram Poormoghadam, Milan Dorscheidt, Sanne Wiekard, Andries Kalsbeek & Chun-Xia Yi

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  1. Han Jiao
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Contributions

H.J. and C.Y. set up the experiments. J.J., M.D. and H.J. performed all the animal housing and time-restricted feeding experiments. H.J., D.P., and M.D. performed spinal cord tissue collection experiment. H.J., M.D., and S.W. performed immunohistochemistry experiment. H.J. performed RNA isolation and PCRs experiments. H.J. and C.Y. conceived the idea and the experimental design. H.J., A.K., and C.Y. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Han Jiao.

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Jiao, H., Jermei, J., Poormoghadam, D. et al. Time-restricted feeding modulates neuron-glial interactions and circadian rhythm in the spinal cord of male Wistar rats fed a high-fat diet. Spinal Cord 63, 437–443 (2025). https://doi.org/10.1038/s41393-025-01106-9

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