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Volume 41 Issue 11
Nov.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(11): 2300-2309

Effect and mechanism of dapagliflozin on gut microbiota in a mouse model of metabolic associated fatty liver disease

DOI: 10.12449/JCH251116
  • 1.

    Department of Clinical Pharmacy，Fuqing Hospital Affiliated to Fujian Medical University，Fuzhou 350300，China

  • 2.

    Department of Science and Education，Fuqing Hospital Affiliated to Fujian Medical University，Fuzhou 350300，China

  • 3.

    Department of Pharmacy，Fuzhou First General Hospital Affiliated with Fujian Medical University，Fuzhou 350009，China

Research funding:

Natural Science Foundation of Fujian Province (2025J011339);

Fuzhou Health Science and Technology Project (2022-S-wq1);

Startup Fund of Scientific Research, Fujian Medical University (2020QH1346)

More Information
  • Corresponding author: DAI Hengfen， hengfendai2011@163.com （ORCID： 0000-0002-2037-4208）
  • Received Date: 2025-06-16
  • Accepted Date: 2025-09-05
  • Published Date: 2025-11-25
    Abstract
  •   Objective  To investigate the effect of dapagliflozin on liver lipid metabolism and gut microecology in mice with metabolic associated fatty liver disease （MAFLD）， and to clarify its potential mechanism.  Methods  A total of 50 male C57 mice were randomly divided into Control group， type 2 diabetes+MAFLD group （MAFLD group）， dapagliflozin group （DAPA group）， meldonium group （THP group）， and dapagliflozin+meldonium group （DAPA+THP group）， with 10 mice in each group. High-fat diet combined with streptozotocin was used to establish a mouse model of MAFLD. Treatment outcomes were assessed based on histopathology and biochemical parameters such as blood glucose and blood lipid levels， and the transcriptomic and metagenomic analyses were used to identify differentially expressed genes and the changes in gut microbiota. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Nemenyi test was used for comparison between two groups.  Results  Histopathological examination showed that the mice in the MAFLD group had excessive lipid deposition and hepatocyte steatosis； compared with the MAFLD group， the DAPA group had a significant improvement in hepatocyte steatosis， while the THP group and the DAPA+THP group had a less significant improvement compared with the DAPA group. Compared with the Control group， the MAFLD group had a significant increase in fasting blood glucose （P<0.05）， significant increases in the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， malondialdehyde， total cholesterol， triglyceride， and low-density lipoprotein cholesterol （P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （P<0.05）. Compared with the MAFLD group， the DAPA group， the THP group， and the DAPA+THP group had significant reductions in the serum levels of ALT and AST （P<0.05）. The results of 16S rRNA sequencing showed that compared with the Control group， the MAFLD group had significant changes in gut microbiota， with an increase in Firmicutes and a reduction in Bacteroidetes， as well as reductions in S24-7 and Erysipelotrichaceae and an increase in Lactobacillaceae. The levels of the above flora were upregulated to normal levels in the DAPA group， the THP group， and the DAPA+THP group. The liver transcriptomic analysis showed that the enriched metabolic pathways included steroid hormone biosynthesis， bile secretion， inflammatory mediator regulation of TRP， fatty acid elongation， and lipid biodegradation processes， and the related genes mainly involved the key targets of lipid metabolism such as Acot2， Angptl4， Scd2， and Npc1l1.  Conclusion  Dapagliflozin can alleviate MAFLD through the pathways such as steroid hormone biosynthesis， bile secretion， inflammatory mediator regulation of TRP， and fatty acid elongation， as well as by regulating gut microbiota homeostasis.

     

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