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Exogenous IGF-1 improves tau pathology and neuronal pyroptosis in high-fat diet mice with cognitive dysfunction

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Abstract

Insulin-like growth factor-1 (IGF-1) improves obesity-induced cognitive dysfunction, but its mechanism is not fully clarified. The aim of the study was to reveal whether IGF-1 treated cognitive dysfunction by improving tau pathology and neuronal pyroptosis in high-fat diet mice. During in vitro experiment, C57BL/6J mice were fed with high-fat diet, and were treated with PEG-IGF-1, IGF-1 receptor blocker AXL1717, HO-1 blocker Znpp IX or their combinations. Cognitive function was evaluated using Morris water maze. Expression of Nrf2, HO-1, p-tau, NLRP3, caspase-1 and IL-1β in hippocampus was determined using western blotting. Pyroptosis rate in hippocampus was measured using flow cytometry. During in vivo experiment, HN-h cells were treated with palmitic acid, pyroptosis blocker nonecrosulfonamide or their combinations. The expression of the proteins and rate of pyroptosis were also measured using western blotting and flow cytometry. During in vitro experiment, high-fat diet mice showed cognitive dysfunction, significant hyperphosphorylation of tau protein and neuronal pyroptosis in hippocampus compared with the sham mice. After exogenous IGF-1 treatment, these abnormalities were reversed and Nrf2/HO-1 signaling pathway was activated. Inhibition of the signaling pathway using AXL1717 or Znpp IX re-deteriorated cognitive function, tau pathology and neuronal pyroptosis in hippocampus. During in vivo experiment, inhibition of pyroptosis using nonecrosulfonamide improved tau pathology in palmitic acid-treated HN-h cells. Exogenous IGF-1 improved tau pathology induced by high-fat diet through inhibition of neuronal pyroptosis and activation of Nrf2/HO-1 signaling pathway.

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The data cannot be shared because this is an ongoing study.

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All analysis is performed by Statistical Product and Service Solutions 19.0.

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Acknowledgements

We want to thank Prof. Jia Qifen from TIANJIN UNIVERSITY (China) for the funding and laboratory support for this project.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychology, Tianjin Anding Hospital, Tianjin, 300074, China

    Guanghong Sui

  2. Department of Rehabilitation, Tianjin Anding Hospital, Tianjin, 300074, China

    Caixia Yang

  3. Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China

    Lu Wang, Xiangyang Xiong, Mengtian Guo & Feng Wang

  4. Department of Psychology, Tianjin Anding Hospital, No. 13, Liulin Road, Hexi District, Tianjin, 300074, China

    Zheng Chen & Feng Wang

Authors
  1. Guanghong Sui
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  2. Caixia Yang
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  3. Lu Wang
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  4. Xiangyang Xiong
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  5. Mengtian Guo
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  6. Zheng Chen
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  7. Feng Wang
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Contributions

Sui Guanghong, Wang Lu, Chen Zheng and Wang Feng conduct study design, literature research and manuscript preparation. Yang Caixia, Guo Mengtian and Xiong Xiangyang carry out experiment and performed data analysis.

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Correspondence to Zheng Chen or Feng Wang.

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The study is approved by the ethics committees of Tianjin Anding Hospital and Tianjin Medical University General Hospital.

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This is an in vivo and in vitro study, and no human subjects are included.

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Sui, G., Yang, C., Wang, L. et al. Exogenous IGF-1 improves tau pathology and neuronal pyroptosis in high-fat diet mice with cognitive dysfunction. Metab Brain Dis 36, 2079–2088 (2021). https://doi.org/10.1007/s11011-021-00787-4

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  • DOI: https://doi.org/10.1007/s11011-021-00787-4

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