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Reduced neurotrophic factor level is the early event before the functional neuronal deficiency in high-fat diet induced obese mice

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Abstract

Neurodegeneration is considered one of the possible complications of high fat diet (HFD) induced obesity. Much evidence has shown the close relationship between HFD and dementia at comparatively later stage of neuronal injury. It is so far not clear that the initial events of neuronal injury resulting from HFD and obesity. In the present research, obese mouse model achieved by 3-month HFD was applied for the investigation of the possible neuronal deficiency before the obvious cognitive decline. We found that 3-month HFD has already increased the average level of body weight of mice. But almost no obvious cognitive defect was observed. At such time point, we detected the cleavage of amyloid precursor protein (APP), including the expression and maturation level of α- and β-secretase and proteolytic fragment soluble APP. Results showed similar readout between HFD and normal diet (ND) mice. Besides, neuronal inflammation and brain-blood barrier permeability were also detected. No obvious changes could be observed between HFD and ND mice. Surprisingly, the first detectable neuronal changes was showed to be the downregulation of some neurotrpic factors, like neuronal growth factor β and brain derived neurotrophic factor, together with the activity of specific receptors, like Trk receptor phosphorylation. All the data piled up indicated that the early neuronal change in HFD induced obese mice was the downregulation of some neurotrophic factors. The results may provide the potential clue to therapeutic and preventive strategy for HFD induced cognitive decline.

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Acknowledgment

This study was funded by Zhejiang Provincial Natural Science Foundation of China (LQ13C090006), National Natural Science Foundation of China (81302781) and Hangzhou Science & Technology Plan Project of China (20140633 B36).

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Authors and Affiliations

  1. School of Medicine, Hangzhou Normal University, Xuelin Street 16#,, Hangzhou, 310036, China

    Huanhuan Wang, Hongping Yin & Xiangmin Kong

  2. College of Life Science, Hangzhou Normal University, Hangzhou, China

    Bing Wang

  3. College of Public Health, Dalian Medical University, Dalian, China

    Guoqing Zhang

  4. Center of Laboratory Animal, Hangzhou Normal University, Hangzhou, China

    Liping Yu

  5. Department of Clinical Laboratory, Women’s Hospital, School of Medicine, Zhejiang University, Zhejiang, China

    Haiying Yuan

  6. College of Science, Hainan Medical School, Hainan, China

    Xingyue Fang & Qibing Liu

  7. College of Basic Medicine, Zhejiang Chinese Medical University, Zhejiang, China

    Cuiqing Liu

  8. Department of Immunology, Nanjing University of Traditional Chinese Medicine, Xianlin Street 138#,, Nanjing, 210023, China

    Liyun Shi

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  1. Huanhuan Wang
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  2. Bing Wang
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  10. Cuiqing Liu
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Correspondence to Huanhuan Wang or Liyun Shi.

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The Animal Care and Use Committee of the School of Medicine, Hangzhou Normal University approved the experimental protocols in this study.

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The authors declare that we have no conflict of interest.

Ethical approval

All of the animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with the approval and monitor of the Animal Care and Use Committee of the School of Medicine, Hangzhou Normal University.

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Wang, H., Wang, B., Yin, H. et al. Reduced neurotrophic factor level is the early event before the functional neuronal deficiency in high-fat diet induced obese mice. Metab Brain Dis 32, 247–257 (2017). https://doi.org/10.1007/s11011-016-9905-z

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  • DOI: https://doi.org/10.1007/s11011-016-9905-z

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