Related Experiment Video
Updated: Jun 29, 2025
Novel In Vivo Micro-Computed Tomography Imaging Techniques for Assessing the Progression of Non-Alcoholic Fatty Liver Disease
Published on: March 24, 2023
Endotoxemia and Platelets: 2 Players of Intrahepatic Microthrombosis in NAFLD
Francesco Violi1, Daniele Pastori2, Pasquale Pignatelli1,2
1Mediterranea Cardiocentro-Napoli, Naples, Italy.
Abstract:
Gut dysbiosis-related intestinal barrier dysfunction with increased translocation of bacterial products such as lipopolysaccharide (LPS) into systemic circulation is emerging as pathogenic factor of nonalcoholic fatty liver disease (NAFLD). Experimental and clinical studies suggested a potential role of LPS as a trigger eliciting in situ liver inflammation upon interaction with its receptor toll-like receptor 4. Also, LPS has been reported to prime platelets to respond to the common agonists indicating that it behaves as a prothrombotic molecule. Of note, recent studies suggested platelet-related intrahepatic thrombosis triggered by LPS as a mechanism implicated in the process of liver inflammation. This review describes: 1) the impact of gut barrier dysfunction and endotoxemia in the process of NAFLD; 2) the relationship between endotoxemia and platelet activation in NAFLD; 3) clinical evidence for the use of antiplatelet drugs in NAFLD/nonalcoholic steatohepatitis patients; and 4) the potential therapeutic approach to modulate endotoxemia and eventually platelet activation.
Insights
Gut dysbiosis contributes to nonalcoholic fatty liver disease (NAFLD) through increased bacterial product translocation. Lipopolysaccharide (LPS) activates platelets, promoting liver inflammation and thrombosis, suggesting antiplatelet therapies for NAFLD.
Area of Science:
- Gastroenterology and Hepatology
- Immunology
- Pathophysiology
Background:
- Gut dysbiosis and intestinal barrier dysfunction increase lipopolysaccharide (LPS) translocation in nonalcoholic fatty liver disease (NAFLD).
- LPS interacts with toll-like receptor 4, initiating liver inflammation and priming platelets, acting as a prothrombotic molecule.
- Platelet activation and intrahepatic thrombosis are implicated in LPS-driven liver inflammation in NAFLD.
Purpose of the Study:
- To review the role of gut barrier dysfunction and endotoxemia in NAFLD pathogenesis.
- To explore the link between endotoxemia and platelet activation in NAFLD.
- To discuss clinical evidence for antiplatelet drugs and potential therapeutic strategies for NAFLD.
Main Methods:
- Literature review of experimental and clinical studies.
- Analysis of the molecular mechanisms involving LPS, TLR4, and platelet activation.
- Examination of clinical trial data on antiplatelet agents in NAFLD/NASH.
Main Results:
- Endotoxemia is a key factor in NAFLD progression.
- LPS significantly activates platelets, contributing to prothrombotic states.
- Evidence supports the investigation of antiplatelet therapies for NAFLD patients.
Conclusions:
- Gut barrier dysfunction and endotoxemia are critical in NAFLD.
- Platelet activation by LPS is a significant mechanism in liver inflammation.
- Modulating endotoxemia and platelet activation offers potential therapeutic avenues for NAFLD.
More Related Videos
Related Concept Videos
01:38Inflammation
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:18Structure and Function of Platelets
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
01:16Clot Retraction and Fibrinolysis