Increased plasmatic NETs by-products in patients in severe obesity

Abstract

Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m² or ≥35 kg/m² + comorbidity) eligible to sleeve gastrectomy. In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable (BMI, waist, hip), glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI (ρ = 0.416, p < 0.05), visceral fat area (ρ = 0.351, p < 0.05), and glycemia (ρ = 0.495, p < 0.001). In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients' systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET's dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.

Figure 1

The concentration of soluble DNA-MPO complexes (a putative marker of in vivo NET generation/catabolism) was determine by ELISA (see methods) in platelet-free plasma samples of patients and of healthy controls (a) and in patients before and after gastric sleeve (b). Two different groups of subjects were observed among the patients studied: those that reduce (Group 1) (c) and those that increased (Group 2) (d) the fraction of plasmatic MPO-DNA complexes after sleeve gastrectomy. (e) The amount of MPO-DNA complexes observed in obese patients were compared to those observed in patients with history of acute myocardial infarction (AMI) or severe coronary artery disease but without previous AMI or unstable angina. In (a–d), each symbol depict the result of a single subject (patient or control). In (a,b), red lines indicates mean ± SD. In (e) ^§§P < 0.001; *P < 0.05; ^##P ≤ 0.001; °P < 0.05; P values were determined by Kruskal-Wallis and Mann-Whitney Tests.