The serine protease KLK7 promotes immune cell infiltration in visceral adipose tissue in obesity.

Summary

Using macrophage-specific KLK7 knockout mice, the study shows that KLK7 drives inflammatory macrophage recruitment and activation in visceral adipose tissue under high-fat diet. Human validation in 1,143 visceral adipose samples linked KLK7 expression to migration/inflammatory pathways, and serum KLK7 correlated with circulating inflammatory markers in obese patients with diabetes.

Key Findings

• Macrophage-specific KLK7 knockout mice had lower systemic inflammation and reduced infiltration/activation of inflammatory macrophages in epididymal adipose tissue under high-fat diet.
• Klk7 deficiency reduced pro-inflammatory gene expression and limited macrophage migration via increased adhesion, hallmarks of obese adipose tissue macrophages.
• In 1,143 human visceral adipose tissue samples, KLK7 expression associated with cellular migration and inflammatory pathways; in a second cohort (n=60), serum KLK7 strongly correlated with circulating inflammatory markers.

Clinical Implications

Targeting KLK7 (e.g., inhibitors/biologics) may reduce visceral adipose inflammation and insulin resistance independent of weight loss; serum KLK7 could aid patient stratification for immunometabolic therapies.

Limitations

• Human data are cross-sectional, limiting causal inference
• No pharmacologic KLK7 inhibition tested in vivo to establish druggability and safety

Future Directions

Develop selective KLK7 inhibitors/biologics and test efficacy/safety in preclinical models and early-phase trials; evaluate serum KLK7 as a biomarker for patient selection and treatment response.