Coagulation Signalling and Metabolic Disorders: Lessons Learned from Animal Models

Area of Science:

• Metabolic disorders
• Inflammation
• Coagulation biology

Background:

• Obesity and nutrient excess trigger metabolic reprogramming and inflammation.
• Chronic inflammation exacerbates insulin resistance and comorbidities.
• Obesity and type 2 diabetes are linked to a hypercoagulable state.

Purpose of the Study:

• To explore the role of coagulation proteases in metabolic inflammation.
• To investigate the link between coagulation pathways and insulin resistance in obesity.
• To identify potential therapeutic targets for thromboinflammatory and cardiometabolic disorders.

Main Methods:

• Review of experimental and clinical studies.
• Analysis of coagulation protease-dependent signaling via protease-activated receptors.
• Examination of factors like tissue factor, protease-activated receptor-2, plasminogen activator inhibitor-1, and thrombomodulin-dependent protein C activation.

Main Results:

• Coagulation protease signaling is associated with inflammation and insulin resistance in diet-induced obesity.
• Increased plasminogen activator inhibitor-1 and fibrin-driven inflammation promote insulin resistance.
• Impaired protein C activation is linked to diabetic kidney disease.

Conclusions:

• Coagulation pathways play a significant role in regulating metabolic inflammation and insulin resistance.
• Understanding these roles is crucial for developing novel treatments for metabolic and cardiometabolic disorders.
• Targeting specific coagulation proteases may offer new therapeutic strategies.