Empagliflozin Attenuates HFD/STZ-induced Liver Fibrosis in Type 2
Diabetes Mellitus Mice by Modulating Gut Microbiota
Purpose: This study aimed to examine the effects of
Empagliflozin on the mice model of HFD/STZ-induced T2DM and liver
fibrosis, and the correlations with gut microbiota. Methods:
The HFD/STZ-induced T2DM and liver fibrosis mice were treated with
Empagliflozin for 6 weeks. After the intervention, OGTT and IPGTT were
performed to assess glucose tolerance and insulin resistance in mice.
The histological chemistry and indicators of liver pathology and liver
fibrosis were assessed. Moreover, 16S rRNA amplicon sequencing for gut
microbiota was performed to explore the changes of gut bacterial
composition. And we analyzed the correlation between alterations in
intestinal microbial composition and liver fibrosis score or glucose
metabolic indicators. Results: 6-week Empagliflozin
intervention improved glucose metabolism, and attenuated liver fibrosis
in HFD/STZ-induced mice, which might be related to the alterations of
gut microbiota. Furthermore, the abundance of Lactobacillus was
increased, while Ruminococcus and Adlercreutzia were
reduced in Empagliflozin-treated mice, which were positively associated
with liver fibrosis and glucose metabolism in correlation analysis.
Conclusion: Empagliflozin ameliorated glucose metabolic
dysfunction and liver fibrosis in HFD/STZ-induced mice, whose effects
might be due to the beneficial balance of gut microbiota composition.
Our study provided evidence and highlighted improvement of gut-liver
axis by inhibition of SGLT2 in T2DM and liver fibrosis.