Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice

Bingyao LIU; Hang YANG; Hongting ZHENG; Xiaoyu LIAO

doi:10.16016/j.2097-0927.202206048

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Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice

Basic Medicine | 更新时间：2026-01-09

- Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice
- Journal of Army Medical University Vol. 44, Issue 23, Pages: 2384-2391(2022)
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院内分泌科
- 作者简介：
- 基金信息：
  
  General Program of Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0465);the National Science Foundation for Distinguished Young Scholars of China(81925007)
- DOI：10.16016/j.2097-0927.202206048
  CLC： Q939.121;R-332;R394.1
- Received：16 June 2022，
  
  Revised：2022-08-28，
  
  Published：15 December 2022
- 稿件说明：
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Bingyao LIU, Hang YANG, Hongting ZHENG, et al. Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice[J]. Journal of Army Medical University, 2022, 44(23): 2384-2391.
DOI：

Bingyao LIU, Hang YANG, Hongting ZHENG, et al. Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice[J]. Journal of Army Medical University, 2022, 44(23): 2384-2391. DOI： 10.16016/j.2097-0927.202206048.

摘要

目的

研究固醇调节元件结合蛋白1c(sterol regulatory element binding protein 1c

SREBP1c)缺失对小鼠肠道菌群结构的影响。

方法

以SREBP1c基因敲除鼠为研究对象，收集纯合敲除型(SREBP1c-KO)和同窝野生型(SREBP1c-WT)的小鼠粪便，采用16S rDNA测序粪便基因组DNA，采用物种分类学分析、多样性指数分析、聚类分析、主成分分析(principal component analysis

PCA)等，比较敲除型和野生型两组小鼠肠道菌群结构的组成差异。检测两组小鼠肝脏脂合成代谢以及肠道屏障的差异。

结果

常规饲养下，SREBP1c基因敲除对小鼠的体重及肝脏总胆固醇含量(total cholesterol

TC)没有显著影响，明显减少肝脏内甘油三酯(triglyceride

TG)含量。α多样性指数(Sobs指数)分析发现，SREBP1c-KO小鼠的肠道菌群多样性显著低于野生型小鼠(

＜0.01)；PCA分析显示，两组小鼠肠道菌群组成有一定程度的差异。在门水平，厚壁菌门与拟杆菌门比值在SREBP1c-KO小鼠肠道中有上升趋势，但没有统计学差异；在属水平，相较于野生型小鼠，SREBP1c-KO小鼠肠道的理研菌属(Rikenella)相对丰度显著减少(

＜0.05)，同时肠道抗菌肽Reg3γ和紧密连接蛋白Occludin表达显著下调。

结论

脂代谢关键调控基因SREBP1c缺失降低小鼠肠道菌群多样性，减少理研菌属相对丰度水平，可能与肠道屏障减弱有关。

Abstract

Objective

To investigate the effects of sterol regulatory element binding protein 1c (SREBP1c) deficiency on the intestinal microbiota in mice.

Methods

SREBP1c knockout (SREBP1c-KO) mice were used as research objects

and the feces of homozygous SREBP1c-KO mice and wild-type littermates (WT) were collected. Subsequently

the fecal genomic DNA was analyzed by 16S rDNA sequencing. The differences of gut microbial composition between the SREBP1c-KO and WT mice were detected and compared using species taxonomy analysis

diversity index analysis

cluster analysis

and principal component analysis (PCA). Moreover

the discrepancies of liver lipid anabolism and intestinal barrier were also investigated between the 2 groups.

Results

Under conventional feeding

SREBP1c knockout had no significant effect on the body weight and total cholesterol (TC) content in the liver of mice

but notably decreased the content of triglyceride (TG) in the liver. α diversity index (Sobs index) analysis showed that the gut microbiota diversity of SREBP1c-KO mice was greatly lower than that of the WT counterparts (

0.01)

and PCA analysis indicated that the gut microbial composition was different between the 2 groups of mice. At the phylum level

the ratio of Firmicutes to Bacteroides presented an upward trend in the intestine of SREBP1c-KO mice

but there was no statistical difference. At the genus level

as compared with the WT group

the relative abundance of Rikenella was significantly reduced in SREBP1c-KO mice (

0.05). Additionally

the expression levels of intestinal barrier associated genes Reg3γ and Occludin were obviously down-regulated in SREBP1c-KO mice.

Conclusion

The deletion of SREBP1c

an important regulator of lipid metabolism

reduces the diversity of intestinal microbiota and the relative abundance of Rikenella in mice

which may be related to the weakening of intestinal barrier.

关键词

Keywords

references

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