The Impact of Bariatric Surgery on Obesity-Associated NETosis, Immune Modulation, and Cardiovascular Risk Reduction.

BACKGROUND

Obesity drives chronic inflammation and a prothrombotic state, contributing to metabolic dysfunction and cardiovascular disease (CVD). Neutrophil extracellular traps (NETs), web-like DNA-protein structures released by neutrophils, trap pathogens through a specialized cellular process called NETosis, which involves chromatin decondensation and cell death. While NETs protect against infection, excessive NET formation promotes tissue damage, insulin resistance, endothelial dysfunction, and thrombosis in obesity. Elevated NETosis fuels systemic inflammation, disrupts insulin signaling, and amplifies platelet aggregation, significantly raising the risk of atherothrombosis and metabolic decline. Given its critical role in obesity-related complications, NETosis presents a promising therapeutic target.

OBJECTIVES

This review explores the mechanistic role of NETosis in obesity-driven thromboinflammation, evaluates the impact of bariatric surgery on NET formation and immune modulation, and discusses therapeutic strategies targeting NETs as potential adjuncts or alternatives to surgery.

METHODS

A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science to identify preclinical and clinical studies examining NETosis, obesity, bariatric surgery, and metabolic inflammation.

RESULTS

Obesity induces neutrophil hyperactivation and excessive NET formation, driving insulin resistance, vascular injury, and hypercoagulability. Elevated plasma NET markers (MPO-DNA, cfDNA, H3Cit) correlate with metabolic dysfunction and cardiovascular risk. Bariatric surgery significantly reduces systemic inflammation, suppresses neutrophil activation, and downregulates NET formation, leading to improved insulin sensitivity, endothelial function, and lower thrombotic risk. These findings suggest bariatric surgery exerts profound immunomodulatory effects beyond weight loss.

CONCLUSIONS

NETosis is a key driver of obesity-associated metabolic and cardiovascular complications. Bariatric surgery effectively reverses NET-driven thromboinflammation, but further research is needed to elucidate its molecular mechanisms and develop NET-targeted therapies as non-surgical alternatives.