ArticleThe Journal of clinical investigation2017
Thrombin promotes diet-induced obesity through fibrin-driven inflammation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 116 citations in OpenAlex.
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- Visualization of intrahepatic activation of coagulation and its contribution to disease progression in mice with acetaminophen-induced acute liver injury.Journal of thrombosis and haemostasis : JTH · 2026Article
- Mouse models to study von Willebrand factor in inflammation: a scoping review.Intensive care medicine experimental · 2026Review
- Soft fibrin matrix instructs macrophage M2 polarization via FABP4-mediated enhancement of fatty acid β-oxidation to alleviate MASH.Cellular and molecular life sciences : CMLS · 2026Article
- From lipoprotein metabolism to blood clotting: Highlights of the 2025 Fredrickson lipid research conference.Journal of lipid research · 2026Article
- Association of Early Heparin Use with Mortality in Cirrhotic Patients: A Retrospective Cohort Study.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- Urokinase Plasminogen Activator Deficiency Delays the Development of Obesity and Metabolic Sequelae.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Distinct fibrin clot characteristics in individuals with severe obesity and metabolic liver disease: 2-year follow-up after bariatric surgery.Research and practice in thrombosis and haemostasis · 2026Article
- Development of a humanized anti-fibrin monoclonal antibody for the treatment of neuroinflammatory and retinal diseases.Journal of neuroinflammation · 2025Article
- Plasma Fibronectin Drives Macrophage Elongation via Integrin β3-Tie2 Axis in Blood Clots.Cancers · 2025Article
- Fibrinogen superfamily proteins: Key regulators in hepatic disorders.World journal of experimental medicine · 2025Review
- Review
- A lipid atlas of the human kidney.Science advances · 2025Article
- Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease.Research and practice in thrombosis and haemostasis · 2025Article
- Venous thrombosis and obesity: from clinical needs to therapeutic challenges.Internal and emergency medicine · 2025Review
- 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
- METTL14 downregulation drives S100A4Signal transduction and targeted therapy · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
Abstract
Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390-396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390-396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients.
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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.