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Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
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Hydronidone Alleviates Metabolic Dysfunction-Associated Fatty Liver Disease by Inhibiting CD36 Expression.

Xin Luo1, Jing-Yi Lu1, Zhen-Yang Shen1

  • 1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 5, 2025
PubMed
Summary

Hydronidone (HDD) effectively treats metabolic dysfunction-associated fatty liver disease (MASLD) by reducing liver fat, inflammation, and fibrosis. It works by inhibiting the CD36 gene, a key factor in MASLD progression.

Keywords:
AMPKCD36Hydronidonemetabolic dysfunction‐associated fatty liver disease (MASLD)

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Pharmacology

Background:

  • Metabolic dysfunction-associated fatty liver disease (MASLD) lacks effective treatments.
  • Investigating novel therapeutic agents for MASLD is crucial.

Purpose of the Study:

  • To evaluate the therapeutic potential of Hydronidone (HDD) in MASLD.
  • To elucidate the molecular mechanisms underlying HDD's effects on MASLD.

Main Methods:

  • MASLD mouse models (HFHC and MCD diets) and cell models (PA-induced hepatocytes/AML12) were established.
  • Animals and cells were treated with varying doses of HDD.
  • Transcriptome sequencing identified CD36 as a key gene.
  • CD36 overexpression was used to validate HDD's mechanism.

Main Results:

  • HDD treatment significantly improved liver steatosis, inflammation, and fibrosis in MASLD models.
  • HDD reduced lipid deposition in hepatocytes and AML12 cells.
  • Transcriptome analysis revealed HDD modulated genes involved in lipid synthesis, inflammation, and fibrosis.
  • Overexpression of CD36 abrogated the therapeutic benefits of HDD.

Conclusions:

  • Hydronidone demonstrates significant therapeutic effects against MASLD.
  • HDD alleviates MASLD progression by inhibiting CD36 expression.
  • HDD represents a promising therapeutic candidate for MASLD treatment.