ArticleThe Journal of pharmacology and experimental therapeutics2014
Thrombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 79 citations in OpenAlex.
- Hepatocyte-independent PAR1-biased signaling controls liver pathology in experimental obesity.Journal of thrombosis and haemostasis : JTH · 2024Article
- The thrombin receptor PAR4 supports visceral adipose tissue inflammation.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.International journal of molecular sciences · 2024Review
- Circulating plasma fibronectin affects tissue insulin sensitivity, adipocyte differentiation, and transcriptional landscape of adipose tissue in mice.Physiological reports · 2024Article
- The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of clinical medicine · 2024Review
- Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.Journal of atherosclerosis and thrombosis · 2023Article
- Integrative analysis of HASMCs gene expression profile revealed the role of thrombin in the pathogenesis of atherosclerosis.BMC cardiovascular disorders · 2023Article
- Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity.iScience · 2022Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Review
- Hypercoagulability in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD): Causes and Consequences.Biomedicines · 2022Review
- Platelets in Non-alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2022Review
- Von Willebrand factor exerts hepatoprotective effects in acute but not chronic cholestatic liver injury in mice.Toxicology · 2021Article
- Dabigatran mitigates cisplatin-mediated nephrotoxicity through down regulation of thrombin pathway.Journal of advanced research · 2021Article
- Targeting von Willebrand factor in liver diseases: A novel therapeutic strategy?Journal of thrombosis and haemostasis : JTH · 2021Review
- Off-target effects of oral anticoagulants - vascular effects of vitamin K antagonist and non-vitamin K antagonist oral anticoagulant dabigatran etexilate.Journal of thrombosis and haemostasis : JTH · 2021Article
- The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy.Research and practice in thrombosis and haemostasis · 2021Article
- Till Death Do Us Part-The Multifaceted Role of Platelets in Liver Diseases.International journal of molecular sciences · 2021Review
- Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma.Cancers · 2021Review
- Short-term high-fat diet intake leads to exacerbation of concanavalin A-induced liver injury through the induction of procoagulation state.Biochemistry and biophysics reports · 2020Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome. Robust coagulation cascade activation is common in obese patients with NAFLD. We identified a critical temporal relationship between thrombin generation and the manifestation of hepatic steatosis, inflammation, and injury in C57BL/6J mice fed a high-fat diet (HFD) for 1, 2, and 3 months. Mice fed a HFD exhibited dramatic increases in hepatocellular injury and inflammation over time. Hepatic fibrin deposition preceded an increase in serum alanine aminotransferase, and the most dramatic changes in liver histopathology occurred in conjunction with a detectable increase in plasma thrombin-antithrombin levels at 3 months. To directly determine whether thrombin activity promotes NAFLD pathogenesis, mice were fed a HFD and simultaneously treated with the direct thrombin inhibitor dabigatran etexilate for 3 months. Notably, dabigatran treatment significantly reduced hepatic fibrin deposition, hepatic inflammation, hepatocellular injury, and steatosis in mice fed a HFD. Of interest, dabigatran treatment also significantly attenuated HFD-induced body weight gain. Gene expression analysis suggested that thrombin potentially drives NAFLD pathogenesis by altering the expression of genes associated with lipid metabolism and bile acid synthesis. Collectively, the results suggest that thrombin activity is central to HFD-induced body weight gain, liver injury, and inflammation and provide the proof-of-principle evidence that pharmacological thrombin inhibition could be effective in limiting NAFLD and associated pathologies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.