Association of SIRT3 gene variation with risk of non-alcoholic fatty liver disease and functional study of the gene in a mouse model

Shuang Zhang; Xiaohui Zhu; Xin Lu; Haiying Fang; Mantian Mi

doi:10.16016/j.1000-5404.201611187

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Association of SIRT3 gene variation with risk of non-alcoholic fatty liver disease and functional study of the gene in a mouse model

更新时间：2026-01-09

- Association of SIRT3 gene variation with risk of non-alcoholic fatty liver disease and functional study of the gene in a mouse model
- Journal of Third Military Medical University Vol. 39, Issue 8, Pages: 737-742(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81502807)
- DOI：10.16016/j.1000-5404.201611187
  CLC：
- Received：22 November 2016，
  
  Published：30 April 2017
- 稿件说明：
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Shuang Zhang, Xiaohui Zhu, Xin Lu, et al. Association of SIRT3 gene variation with risk of non-alcoholic fatty liver disease and functional study of the gene in a mouse model[J]. Journal of Third Military Medical University, 2017, 39(8): 737-742.
DOI：

Shuang Zhang, Xiaohui Zhu, Xin Lu, et al. Association of SIRT3 gene variation with risk of non-alcoholic fatty liver disease and functional study of the gene in a mouse model[J]. Journal of Third Military Medical University, 2017, 39(8): 737-742. DOI： 10.16016/j.1000-5404.201611187.

摘要

Abstract

Objective

To investigate the association between silent mating-type information regulation 2 homolog 3 (SIRT3) gene variation and the risk of non-alcoholic fatty liver disease (NAFLD) and explore the gain-of-function effect of SIRT3 in a mouse model of NAFLD.

Methods

Blood samples were collected from 374 patients with NAFLD and 372 health control subjects at the Health Examination Center of Southwest Hospital from March 2014 to March 2015. Genome DNA was extracted from the samples for rs11246020 genotyping using Mass-Array system

and the genotype distribution of rs11246020 was analyzed. A plasmid carrying human SIRT3 gene was transfected in a mouse model of NAFLD

and in 8 weeks later

the biochemical indexes and levels of inflammatory cytokines in the serum and liver of the mice were evaluated; the pathology of the liver tissues was observed with HE and oil Red O staining

and the expression levels of Pparα

Acox1

cpt1a

and cpt1b mRNAs and SIRT3 protein in the liver were detected using real-time PCR and Western blotting.

Results

Compared with the control group

the patients with NAFLD showed a significantly decreased frequency of GA+AA genotype and an increased frequency of GG genotype of rs11246020 in SIRT3 gene (

0.05). In the mouse model of NAFLD

over-expression of human SIRT3 in the liver significantly reduced the levels of total cholesterol

triglyceride

and free fatty acids in both the serum and the liver (

0.05) and obviously lowered the expression levels of Pparα and Acox1 mRNAs in the liver (

0.05). Pathological examination of the liver tissue from the mice with SIRT3 over-expression revealed significantly reduced accumulation of fat vacuoles and lipid droplets. SIRT3 over-expression also effectively controlled the weight gain in the mice (

0.05).

Conclusion

SIRT3 gene variation is associated with the risk of NAFLD

and SIRT3 over-expression improves NALFD in mice possibly by modulating fatty acid metabolism.

关键词

Keywords

references

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