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Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice

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Abstract

Purpose

Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion.

Methods

To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks.

Results

Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion.

Conclusion

Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81571395, 81373075 and 81371748).

Funding

This study was funded by the National Natural Science Foundation of China (81571395, 81373075 and 81371748).

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Authors and Affiliations

  1. Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Rongying Ou, Jia Liu, Mingfen Lv, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao & Yunsheng Xu

  2. Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Rongying Ou

  3. Department of Dermatovenereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Jia Liu, Mingfen Lv, Jingying Wang, Jinmeng Wang, Li Zhu & Yunsheng Xu

  4. Division of PET/CT, Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Liang Zhao

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  1. Rongying Ou
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  2. Jia Liu
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  3. Mingfen Lv
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  4. Jingying Wang
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  5. Jinmeng Wang
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  6. Li Zhu
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  7. Liang Zhao
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  8. Yunsheng Xu
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Correspondence to Liang Zhao or Yunsheng Xu.

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The authors declare that they have no competing interests.

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Procedures involving the animal experiments were approved by the Wenzhou Medical University Animal Policy and Welfare Committee.

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Ou, R., Liu, J., Lv, M. et al. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice. Endocrine 57, 72–82 (2017). https://doi.org/10.1007/s12020-017-1323-4

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