SREBP1c缺失对小鼠肠道菌群的影响

刘冰瑶; 杨航; 郑宏庭; 廖晓玉

doi:10.16016/j.2097-0927.202206048

您当前的位置：

首页 >

文章列表页 >

SREBP1c缺失对小鼠肠道菌群的影响

基础医学 | 更新时间：2026-01-09

- SREBP1c缺失对小鼠肠道菌群的影响
- Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice
- 陆军军医大学学报 2022年44卷第23期页码：2384-2391
- 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：
  
  [郑宏庭，E-mail: fnf7703@hotmail.comZHENG Hongting, E-mail: fnf7703@hotmail.com
  [廖晓玉，E-mail: liaoxiaoyu2010@163.comLIAO Xiaoyu, E-mail: liaoxiaoyu2010@163.com
- 基金信息：
  
  重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0465);国家自然科学基金杰青项目(81925007)
- DOI：10.16016/j.2097-0927.202206048
  中图分类号： Q939.121;R-332;R394.1
- 收稿：2022-06-16，
  
  修回：2022-08-28，
  
  纸质出版：2022-12-15
- 稿件说明：
移动端阅览
刘冰瑶, 杨航, 郑宏庭, 等. SREBP1c缺失对小鼠肠道菌群的影响[J]. 陆军军医大学学报, 2022,44(23):2384-2391.

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.
刘冰瑶, 杨航, 郑宏庭, 等. SREBP1c缺失对小鼠肠道菌群的影响[J]. 陆军军医大学学报, 2022,44(23):2384-2391. DOI： 10.16016/j.2097-0927.202206048.

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

ECKBURG P B, BIK E M, BERNSTEIN C N, et al . Diversity of the human intestinal microbial flora[J ] . Science, 2005, 308(5728): 1635-1638. DOI:10.1126/science.1110591.

BRUCE-KELLER A J, SALBAUM J M, BERTHOUD H R. Harnessing gut microbes for mental health: getting from here to there[J]. Biol Psychiatry, 2018, 83(3): 214-223. DOI:10.1016/j.biopsych.2017.08.014.

GILL S R, POP M, DEBOY R T, et al . Metagenomic analysis of the human distal gut microbiome[J ] . Science, 2006, 312(5778): 1355-1359. DOI:10.1126/science.1124234.

SCHER J U, ABRAMSON S B. The microbiome and rheumatoid arthritis[J]. Nat Rev Rheumatol, 2011, 7(10): 569-578. DOI:10.1038/nrrheum.2011.121.

CHU H, KHOSRAVI A, KUSUMAWARDHANI I P, et al . Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease[J ] . Science, 2016, 352(6289): 1116-1120. DOI:10.1126/science.aad9948.

KARLSSON F H, TREMAROLI V, NOOKAEW I, et al . Gut metagenome in European women with normal, impaired and diabetic glucose control[J ] . Nature, 2013, 498(7452): 99-103. DOI:10.1038/nature12198.

LYNCH S V, PEDERSEN O. The human intestinal microbiome in health and disease[J]. N Engl J Med, 2016, 375(24): 2369-2379. DOI:10.1056/NEJMra1600266.

SHAPIRO H, SUEZ J, ELINAV E. Personalized microbiome-based approaches to metabolic syndrome management and prevention[J]. J Diabetes, 2017, 9(3): 226-236. DOI:10.1111/1753-0407.12501.

LEEMING E R, JOHNSON A J, SPECTOR T D, et al . Effect of diet on the gut microbiota: rethinking intervention duration[J ] . Nutrients, 2019, 11(12): E2862. DOI:10.3390/nu11122862.

GACESA R, KURILSHIKOV A, VICH VILA A, et al . Environmental factors shaping the gut microbiome in a Dutch population[J ] . Nature, 2022, 604(7907): 732-739. DOI:10.1038/s41586-022-04567-7.

KURILSHIKOV A, MEDINA-GOMEZ C, BACIGALUPE R, et al . Large-scale association analyses identify host factors influencing human gut microbiome composition[J ] . Nat Genet, 2021, 53(2): 156-165. DOI:10.1038/s41588-020-00763-1.

HAAS J T, MIAO J, CHANDA D, et al . Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression[J ] . Cell Metab, 2012, 15(6): 873-884. DOI:10.1016/j.cmet.2012.05.002.

LEE G, KIM Y Y, JANG H, et al . SREBP1c-PARP1 axis tunes anti-senescence activity of adipocytes and ameliorates metabolic imbalance in obesity[J ] . Cell Metab, 2022, 34(5): 702-718. e5. DOI:10 .1016/j.cmet.2022.03.010.

NGUYEN T T P, KIM D Y, LEE Y G, et al . SREBP-1c impairs ULK1 sulfhydration-mediated autophagic flux to promote hepatic steatosis in high-fat-diet-fed mice[J ] . Mol Cell, 2021, 81(18): 3820-3832. e7. DOI:10.1016/j.molcel.2021.06.003.

BÄCKHED F, DING H, WANG T, et al . The gut microbiota as an environmental factor that regulates fat storage[J ] . Proc Natl Acad Sci USA, 2004, 101(44): 15718-15723. DOI:10.1073/pnas.0407076101.

DUBIN K, CALLAHAN M K, REN B Y, et al . Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis[J ] . Nat Commun, 2016, 7: 10391. DOI:10.1038/ncomms10391.

ZHOU W Y, SAILANI M R, CONTREPOIS K, et al . Longitudinal multi-omics of host-microbe dynamics in prediabetes[J ] . Nature, 2019, 569(7758): 663-671. DOI:10.1038/s41586-019-1236-x.

DANIEL H, GHOLAMI A M, BERRY D, et al . High-fat diet alters gut microbiota physiology in mice[J ] . ISME J, 2014, 8(2): 295-308. DOI:10.1038/ismej.2013.155.

TAVELLA T, RAMPELLI S, GUIDARELLI G, et al . Elevated gut microbiome abundance of Christensenellaceae, Porphyromonadaceae and Rikenellaceae is associated with reduced visceral adipose tissue and healthier metabolic profile in Italian elderly[J ] . Gut Microbes, 2021, 13(1): 1-19. DOI:10.1080/19490976.2021.1880221..

SHI H J, CHANG Y G, GAO Y, et al . Dietary fucoidan of Acaudina molpadioides alters gut microbiota and mitigates intestinal mucosal injury induced by cyclophosphamide[J ] . Food Funct, 2017, 8(9): 3383-3393. DOI:10.1039/c7fo00932a..

GURUNG M, LI Z P, YOU H, et al . Role of gut microbiota in type 2 diabetes pathophysiology[J ] . EBioMedicine, 2020, 51: 102590. DOI:10.1016/j.ebiom.2019.11.051.

KOLODZIEJCZYK A A, ZHENG D P, SHIBOLET O, et al . The role of the microbiome in NAFLD and NASH[J ] . EMBO Mol Med, 2019, 11(2): e9302. DOI:10.15252/emmm.201809302.

TILG H, ZMORA N, ADOLPH T E, et al . The intestinal microbiota fuelling metabolic inflammation[J ] . Nat Rev Immunol, 2020, 20(1): 40-54. DOI:10.1038/s41577-019-0198-4.

SHIN N R, LEE J C, LEE H Y, et al . An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice[J ] . Gut, 2014, 63(5): 727-735. DOI:10.1136/gutjnl-2012-303839..

WU G D, CHEN J, HOFFMANN C, et al . Linking long-term dietary patterns with gut microbial enterotypes[J ] . Science, 2011, 334(6052): 105-108. DOI:10.1126/science.1208344.

LIAO X Y, SONG L Y, ZENG B H, et al . Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis[J ] . EBioMedicine, 2019, 44: 665-674. DOI:10.1016/j.ebiom.2019.03.057.

UDAYAN S, STAMOU P, CRISPIE F, et al . Identification of gut bacteria such as Lactobacillus johnsonii that disseminate to systemic tissues of wild type and MyD88-/- mice[J ] . Gut Microbes, 2022, 14(1): 2007743. DOI:10.1080/19490976.2021.2007743..

SU S Y, TIAN H M, JIA X, et al . Mechanistic insights into the effects of SREBP1c on hepatic stellate cell and liver fibrosis[J ] . J Cell Mol Med, 2020, 24(17): 10063-10074. DOI:10.1111/jcmm.15614.

DAI J J, JIANG M J, HU Y Y, et al . Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair[J ] . JCI Insight, 2021, 6(2): 138584. DOI:10.1172/jci.insight.138584.

XU X Z, GAO Z Z, YANG F Q, et al . Antidiabetic effects of Gegen Qinlian Decoction via the gut microbiota are attributable to its key ingredient berberine[J ] . Genomics Proteomics Bioinformatics, 2020, 18(6): 721-736. DOI:10.1016/j.gpb.2019.09.007.

ROMANO K A, MARTINEZ-DEL CAMPO A, KASAHARA K, et al . Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption[J ] . Cell Host Microbe, 2017, 22(3): 279-290. e7. DOI:10.1016/j.chom.2017.07.021.

WANG X Y, LI Y, CHEN W J, et al . Transcriptome-wide reprogramming of N6-methyladenosine modification by the mouse microbiome[J ] . Cell Res, 2019, 29(2): 167-170. DOI:10.1038/s41422-018-0127-2.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

小檗碱调节肠道菌群改善小鼠药物性肝损伤

限时进食通过影响再生胰岛衍生蛋白3γ与肠道菌群缓解小鼠结肠炎

2.65 GHz射频长期辐射对小鼠机体炎症反应和肠道微生态的影响

昼夜节律紊乱人群肠道菌群特征及其与认知的相关性研究

胆囊切除术与肠道菌群组成及其功能变化关系的研究