转录因子KLF16对非酒精性脂肪肝病脂质代谢的影响

蔡冠军; 崔心远; 李文毅; 彭文芳

doi:10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2024.0410

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转录因子KLF16对非酒精性脂肪肝病脂质代谢的影响

基础研究 | 更新时间：2024-07-30

- 转录因子KLF16对非酒精性脂肪肝病脂质代谢的影响
- Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease
- 中山大学学报（医学科学版） 2024年45卷第4期页码：582-592
- 作者机构：
  
  1.上海交通大学医学院附属同仁医院内分泌内科，上海，200000
  2.上海交通大学医学院虹桥国际医学研究院，上海，200000
- 作者简介：
  
  蔡冠军，第一作者，研究方向：内分泌与代谢病，E-mail：ad_caiguanjun@163.com
- 基金信息：
  
  上海市同仁医院科研型人才“同仁英才”基金(TRKYRC-yc202202)
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2024.0410
  中图分类号： R589.2
- 纸质出版日期：2024-07-20，
  
  收稿日期：2024-03-31，
  
  录用日期：2024-06-27
- 稿件说明：
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蔡冠军,崔心远,李文毅等.转录因子KLF16对非酒精性脂肪肝病脂质代谢的影响[J].中山大学学报（医学科学版）,2024,45(04):582-592.

CAI Guanjun,CUI Xinyuan,LI Wenyi,et al.Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):582-592.
蔡冠军,崔心远,李文毅等.转录因子KLF16对非酒精性脂肪肝病脂质代谢的影响[J].中山大学学报（医学科学版）,2024,45(04):582-592. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2024.0410.

CAI Guanjun,CUI Xinyuan,LI Wenyi,et al.Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):582-592. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2024.0410.

摘要

目的

探究转录因子KLF16在非酒精性脂肪肝病（NAFLD）中的表达改变以及其对脂质代谢的影响。

方法

通过高脂饮食诱导小鼠构建NAFLD的动物模型。将小鼠分为正常饮食组（ND）和高脂饮食组（HFD）；油酸诱导小鼠肝脏原代细胞构建NAFLD细胞模型。将细胞分为对照组（Control）和油酸诱导组（OA）；实时荧光定量PCR （RT-qPCR）和蛋白免疫印迹技术（Western blot）方法检测NAFLD动物和细胞模型中KLF16的表达变化。通过小鼠尾静脉注射腺相关病毒（AAV）和细胞瞬时转染siRNA构建KLF16敲减的体内外模型。油红染色，苏木素伊红染色（HE）等方法检测KLF16敲减前后细胞NAFLD模型中脂质沉积的变化；RT-qPCR方法检测KLF16敲减前后细胞和动物NAFLD模型中脂质代谢关键基因表达的变化；Western blot方法检测KLF16敲减前后细胞NAFLD模型中内质网应激蛋白的表达。

结果

KLF16在HFD组和OA组表达水平上调，KLF16敲低后OA组脂质沉积加重，肝细胞内TC水平组间无变化（

0.05），TG水平出现不同程度的上升（

0.05，

0.001）。同时引发脂质代谢关键基因的改变，KLF16表达改变也引发OA组中内质网应激蛋白表达改变。

结论

转录因子KLF16可能通过内质网应激缓解非酒精性脂肪肝病的脂质沉积。

Abstract

Objective

To explore the expression of transcription factor KLF16 in nonalcoholic fatty liver disease （NAFLD） and its effect on lipid metabolism.

Methods

An animal model of NAFLD was constructed in mice induced by a high-fat diet. The mice were divided into normal diet group （ND） and high fat diet group （HFD）. NAFLD cell model was constructed by primary mouse liver cells induced by oleic acid. The cells were divided into control group （Control group） and oleic acid induction group （OA group）. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blot were used to detect KLF16 expression in NAFLD animal and cell models. In vitro and in vivo models of KLF16 knockdown were constructed by injection of adeno-associated virus （AAV） into mouse tail veins and transient transfection of cell siRNA. Hematoxylin-eosin staining （HE） and other methods were used to detect changes in lipid deposition in NAFLD models before and after KLF16 knockout. RT-qPCR was used to detect the expression of key genes of lipid metabolism in both cellular and animal NAFLD models before and after KLF16 knockdown. Western blot assay was used to detect the expression of endoplasmic reticulum stress protein in NAFLD model before and after KLF16 knockdown.

Results

The expression level of KLF16 was up-regulated in HFD group and OA group， and lipid deposition was increased in OA group after KLF16 was depressed. There was no change in TC level in hepatocytes between groups （

0.05）， and TG level was increased in different degrees （

0.05，

0.001）. At the same time， the change of KLF16 expression also caused the change of ER stress

protein expression in OA group.

Conclusion

The transcription factor KLF16 may alleviate lipid deposition in nonalcoholic fatty liver disease by endoplasmic reticulum stress.

关键词

克里佩尔样因子16内质网应激非酒精性脂肪肝病脂质代谢腺相关病毒基因敲减

Keywords

Krüppel-like factor 16endoplasmic reticulum stressnonalcoholic fatty liver diseaselipid metabolismadeno-associated virusgene knockdown

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