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Updated: Jun 15, 2026
In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
Published on: July 19, 2024
[Pathogenesis and treatment of non-alcoholic fatty liver disease]
Ping Xie1, Xin-xi Zhou, Qin Zhang
1Department of Liver Diseases, Shanghai Public Clinical Health Center, Fudan University, Shanghai 201508, China.
Abstract:
In order to explore the pathogenesis of non-alcoholic fatty liver disease (NAFLD), and to find the best evidence for clinical practice, recent literature about the pathogenesis and treatment of NAFLD was analyzed, and it was found that the generation of reactive oxygen species (ROS) is the most important factor in development of NAFLD. Based on insulin resistance (IR), generation of ROS is a central link in the course of "two hits". Other factors, such as leptin resistance, caspase-3, Fas and its ligand, peripheral natural killer T cells, cyclooxygenase-2, metabolic nuclear receptors, hepatic deposition of iron, ferritin, haptoglobin, retinol binding protein 4, imbalance of intestinal flora, mitochondrial dysfunction and endoplasmic reticulum stress, also contribute to the progress of NAFLD. In the treatment of NAFLD, beside the conventionally used methods such as IR improvement, antioxidation and lipid metabolism improvement, other medicines such as nuclear metabolism ligands or activators, iron-chelating agents and syndrome differentiation treatment in traditional Chinese medicine also have good efficacy.
Insights
Reactive oxygen species (ROS) drive non-alcoholic fatty liver disease (NAFLD) pathogenesis, linked to insulin resistance (IR). Novel treatments target ROS, iron, and utilize traditional Chinese medicine for improved NAFLD management.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Context:
- Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern.
- Understanding NAFLD pathogenesis is crucial for effective clinical practice.
- Existing literature provides a foundation for exploring NAFLD's complex mechanisms.
Purpose:
- To analyze recent literature on NAFLD pathogenesis and treatment.
- To identify key factors contributing to NAFLD development.
- To evaluate evidence-based therapeutic strategies for NAFLD.
Summary:
- Reactive oxygen species (ROS) generation is identified as the primary driver of NAFLD, intricately linked with insulin resistance (IR) in the "two-hit" model.
- Multiple factors including leptin resistance, immune cell involvement, metabolic dysregulation, and gut microbiome imbalance contribute to NAFLD progression.
- Effective NAFLD treatments encompass conventional approaches (IR improvement, antioxidation, lipid management) and emerging therapies (nuclear receptor modulators, iron chelation, traditional Chinese medicine).
Impact:
- Highlights the central role of ROS in NAFLD, guiding future research.
- Provides a comprehensive overview of contributing factors for a holistic understanding of NAFLD.
- Informs clinical practice by validating established treatments and suggesting novel therapeutic avenues for NAFLD.
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