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GLUT5-Driven Gut-Liver Axis Injury Mediating Olanzapine-Induced NAFLD and Dapagliflozin Intervention

Xiao Chen1, Yue Zhang2, Jie Wang2

  • 1School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.

Drug Design, Development and Therapy
|March 5, 2026
PubMed
Abstract

Insights

Olanzapine causes non-alcoholic fatty liver disease (NAFLD) by damaging the gut-liver axis via GLUT5/AMPK/mTOR. Dapagliflozin intervention reverses this damage, offering a potential treatment for olanzapine-induced NAFLD.

Area of Science:

  • Pharmacology
  • Hepatology
  • Gastroenterology

Background:

  • Olanzapine is a significant cause of drug-induced non-alcoholic fatty liver disease (NAFLD).
  • The precise mechanism underlying olanzapine-induced NAFLD remains unclear.
  • Dapagliflozin has demonstrated potential therapeutic effects in NAFLD patients.

Purpose of the Study:

  • To elucidate the mechanism of olanzapine-induced NAFLD.
  • To investigate the intervention effects of dapagliflozin on olanzapine-induced NAFLD.
  • To explore the role of the gut-liver axis in olanzapine-induced NAFLD.

Main Methods:

  • Utilized a wistar rat model with control, olanzapine (OLA), and dapagliflozin intervention (DAP) groups over 12 weeks.
  • Employed transcriptomics, molecular biology, and pathological staining to analyze liver and intestinal tissues.
  • Investigated the expression of GLUT5 and the AMPK/mTOR signaling pathway.

Main Results:

  • Olanzapine significantly upregulated GLUT5 expression in the liver and intestine, indicating gut-liver axis injury.
  • The GLUT5/AMPK/mTOR pathway was identified as the mediator of olanzapine-induced gut-liver axis injury and NAFLD.
  • Dapagliflozin intervention successfully reversed GLUT5/AMPK/mTOR pathway activation, improving intestinal barrier function, NAFLD, and hepatic fibrosis.

Conclusions:

  • Discovered that the GLUT5/AMPK/mTOR pathway drives gut-liver axis injury in olanzapine-induced NAFLD.
  • Demonstrated that dapagliflozin intervention can ameliorate olanzapine-induced NAFLD by reversing GLUT5/AMPK/mTOR-mediated gut-liver axis injury.
  • Provided novel insights into olanzapine-induced NAFLD pathogenesis and a potential therapeutic strategy for clinical intervention.
Keywords:
GLUT5NAFLDdapagliflozingut-liver axisolanzapine

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