ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO622

Microbiota Dysbiosis Contributes to Liver Injury in Apolipoprotein Knockout Mice Through the Disruption of Cholesterol Homeostasis

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic

Authors

  • Chen, Peipei, Institute of Nephrology,Zhongda Hospital,Southeast University, Nan Jing City, China
  • Ma, Kun ling, Institute of Nephrology,Zhongda Hospital,Southeast University, Nan Jing City, China
  • Zhang, Yang, Institute of Nephrology,Zhongda Hospital,Southeast University, Nan Jing City, China
  • Wang, Gui hua, Institute of Nephrology,Zhongda Hospital,Southeast University, Nan Jing City, China
  • Hu, Zebo, Institute of Nephrology,Zhongda Hospital,Southeast University, Nan Jing City, China
  • Lu, Jian, Institute of Nephrology, Zhongda Hospital, Nanjing, JIANGSU , China
  • Lu, Chenchen, Institute of Nephrology, Zhong Da Hospital, Nan Jing City, China
Background

Our previous studies demonstrated that cholesterol accumulation in liver contributes to the progression of nonalcoholic fatty liver disease (NAFLD). The exact mechanisms of this process have not been completely explained. This study aimed to investigate the effects of gut microbiota on cholesterol homeostasis of liver in NAFLD.

Methods

Broad-spectrum antibiotics were used to eliminate gut microbiota in high-fat diet (HFD) induced apolipoprotein E knockout mice. Feces were collected and proportions of microbiota were analyzed by 16S rRNA gene sequencing. Serum lipids were examined by automatic analyzer. Cholesterol accumulation in liver was detected by Oil red O staining, Filipin staining, and intracellular free cholesterol quantitative assay. The expressions of molecules involved in cholesterol homeostasis were measured by immunohistochemical staining and Western blotting.

Results

As demonstrated by 16S rRNA gene sequencing,the abundance of Desulfovibrio was significantly increased in HFD mice while the abundance of Bacteroidetes, Ruminococcaceae, and Lactobacillus decreased when compared with the control. Antibiotics treatment effectively depleted gut microbiota in HFD mice. Interestingly, depletion of gut microbiota significantly decreased total cholesterol(TC) and low density lipoprotein(LDL) in the plasma and lipid accumulation in livers of HFD fed mice. Immunohistochemical staining and Western blotting further demonstrated that the expressions of LDL receptor (LDLR) and 3-hydroxy-3-methyl-glutaryl-CoA reductase(HMGR) were downregulated in antibiotics delpleted HFD fed mice.

Conclusion

Our findings demonstrated that gut microbiota dysbiosis may be responsible for the liver injury in NAFLD by disrupting cholesterol homeostasis. This study provides more evidence for that modification of gut microbita dysbiosis is suggested to be a potential target for NAFLD therapy.